House, M.D. is primarily based on which literary detective?

House, M.D. is primarily based on Sherlock Holmes.

Gregory House was designed as a medical counterpart to Arthur Conan Doyle’s detective. Both characters are exceptionally observant, skeptical of conventional explanations, and willing to use unconventional reasoning to solve difficult cases. House’s surname also echoes Holmes’s, and Wilson parallels Holmes’s friend Dr. John Watson.

The medical cases function like detective mysteries. Symptoms are clues, diagnoses are hypotheses, and the final explanation usually emerges after House identifies an overlooked detail. The show also includes references and character parallels that reinforce the connection.

House is not a direct adaptation of one Holmes story. Instead, the series transfers the detective’s investigative structure and personality traits into a hospital setting. That distinction explains why the show can be inspired by Holmes while remaining an original medical drama.