Comfort Inn is a subdivision of Choice Hotels International, a hospitality holding corporation which is affiliated with several hotel brands and is based in Silver Spring, Maryland. The company was started in 1939 in Maryland as Quality Courts United, a referral chain consisting of about seven motel owners. Later, the motel chain operated simply under the name Quality Motels from 1969–71 and Quality Inns since 1972. In 1982, Quality Inns pioneered segmentation in the lodging industry by introducing Comfort Inns and Quality Royale. Comfort Inn competes with such chains such as AmericInn Hotels, Baymont Inn & Suites, and Fairfield Inn by Marriott.

In "Road to Europe", after their camel Chucky dies from exhaustion as they try to make their way to London so Stewie Griffin can be on Jolly Farm Revue, Brian Griffin proposes they cut Chucky open to survive the freezing night temperatures. After Stewie crawls inside, Brian notices a nearby Comfort Inn where they take shelter for the night and then plan the next leg of their trip the following morning.

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