diff --git a/homeassistant/components/opentherm_gw/__init__.py b/homeassistant/components/opentherm_gw/__init__.py
index 7c27eeceede..cdf360c8795 100644
--- a/homeassistant/components/opentherm_gw/__init__.py
+++ b/homeassistant/components/opentherm_gw/__init__.py
@@ -1,9 +1,11 @@
 """Support for OpenTherm Gateway devices."""
+import asyncio
 from datetime import date, datetime
 import logging
 
 import pyotgw
 import pyotgw.vars as gw_vars
+from serial import SerialException
 import voluptuous as vol
 
 from homeassistant.config_entries import SOURCE_IMPORT, ConfigEntry
@@ -23,6 +25,7 @@ from homeassistant.const import (
     Platform,
 )
 from homeassistant.core import HomeAssistant, ServiceCall
+from homeassistant.exceptions import ConfigEntryNotReady
 from homeassistant.helpers import config_validation as cv, device_registry as dr
 from homeassistant.helpers.dispatcher import async_dispatcher_send
 from homeassistant.helpers.typing import ConfigType
@@ -37,6 +40,7 @@ from .const import (
     CONF_PRECISION,
     CONF_READ_PRECISION,
     CONF_SET_PRECISION,
+    CONNECTION_TIMEOUT,
     DATA_GATEWAYS,
     DATA_OPENTHERM_GW,
     DOMAIN,
@@ -107,8 +111,15 @@ async def async_setup_entry(hass: HomeAssistant, config_entry: ConfigEntry) -> b
 
     config_entry.add_update_listener(options_updated)
 
-    # Schedule directly on the loop to avoid blocking HA startup.
-    hass.loop.create_task(gateway.connect_and_subscribe())
+    try:
+        await asyncio.wait_for(
+            gateway.connect_and_subscribe(),
+            timeout=CONNECTION_TIMEOUT,
+        )
+    except (asyncio.TimeoutError, ConnectionError, SerialException) as ex:
+        raise ConfigEntryNotReady(
+            f"Could not connect to gateway at {gateway.device_path}: {ex}"
+        ) from ex
 
     await hass.config_entries.async_forward_entry_setups(config_entry, PLATFORMS)
 
@@ -428,6 +439,9 @@ class OpenThermGatewayDevice:
     async def connect_and_subscribe(self):
         """Connect to serial device and subscribe report handler."""
         self.status = await self.gateway.connect(self.device_path)
+        if not self.status:
+            await self.cleanup()
+            raise ConnectionError
         version_string = self.status[gw_vars.OTGW].get(gw_vars.OTGW_ABOUT)
         self.gw_version = version_string[18:] if version_string else None
         _LOGGER.debug(
diff --git a/homeassistant/components/opentherm_gw/config_flow.py b/homeassistant/components/opentherm_gw/config_flow.py
index 3f91496adab..c3a955b2387 100644
--- a/homeassistant/components/opentherm_gw/config_flow.py
+++ b/homeassistant/components/opentherm_gw/config_flow.py
@@ -26,6 +26,7 @@ from .const import (
     CONF_READ_PRECISION,
     CONF_SET_PRECISION,
     CONF_TEMPORARY_OVRD_MODE,
+    CONNECTION_TIMEOUT,
 )
 
 
@@ -62,15 +63,21 @@ class OpenThermGwConfigFlow(config_entries.ConfigFlow, domain=DOMAIN):
                 otgw = pyotgw.OpenThermGateway()
                 status = await otgw.connect(device)
                 await otgw.disconnect()
+                if not status:
+                    raise ConnectionError
                 return status[gw_vars.OTGW].get(gw_vars.OTGW_ABOUT)
 
             try:
-                res = await asyncio.wait_for(test_connection(), timeout=10)
-            except (asyncio.TimeoutError, SerialException):
+                await asyncio.wait_for(
+                    test_connection(),
+                    timeout=CONNECTION_TIMEOUT,
+                )
+            except asyncio.TimeoutError:
+                return self._show_form({"base": "timeout_connect"})
+            except (ConnectionError, SerialException):
                 return self._show_form({"base": "cannot_connect"})
 
-            if res:
-                return self._create_entry(gw_id, name, device)
+            return self._create_entry(gw_id, name, device)
 
         return self._show_form()
 
diff --git a/homeassistant/components/opentherm_gw/const.py b/homeassistant/components/opentherm_gw/const.py
index a5042628529..d72469759f1 100644
--- a/homeassistant/components/opentherm_gw/const.py
+++ b/homeassistant/components/opentherm_gw/const.py
@@ -25,6 +25,8 @@ CONF_READ_PRECISION = "read_precision"
 CONF_SET_PRECISION = "set_precision"
 CONF_TEMPORARY_OVRD_MODE = "temporary_override_mode"
 
+CONNECTION_TIMEOUT = 10
+
 DATA_GATEWAYS = "gateways"
 DATA_OPENTHERM_GW = "opentherm_gw"
 
diff --git a/homeassistant/components/opentherm_gw/strings.json b/homeassistant/components/opentherm_gw/strings.json
index f53ffeda6f6..a80a059481d 100644
--- a/homeassistant/components/opentherm_gw/strings.json
+++ b/homeassistant/components/opentherm_gw/strings.json
@@ -12,7 +12,8 @@
     "error": {
       "already_configured": "[%key:common::config_flow::abort::already_configured_device%]",
       "id_exists": "Gateway id already exists",
-      "cannot_connect": "[%key:common::config_flow::error::cannot_connect%]"
+      "cannot_connect": "[%key:common::config_flow::error::cannot_connect%]",
+      "timeout_connect": "[%key:common::config_flow::error::timeout_connect%]"
     }
   },
   "options": {
diff --git a/tests/components/opentherm_gw/test_config_flow.py b/tests/components/opentherm_gw/test_config_flow.py
index 46d53bc54b5..080e9a96d58 100644
--- a/tests/components/opentherm_gw/test_config_flow.py
+++ b/tests/components/opentherm_gw/test_config_flow.py
@@ -164,7 +164,7 @@ async def test_form_connection_timeout(hass):
         )
 
     assert result2["type"] == "form"
-    assert result2["errors"] == {"base": "cannot_connect"}
+    assert result2["errors"] == {"base": "timeout_connect"}
     assert len(mock_connect.mock_calls) == 1