House M.D. was chiefly inspired by which fictional detective?

House M.D. was chiefly inspired by Sherlock Holmes.

Gregory House parallels Holmes in several deliberate ways: both are exceptionally perceptive investigators, rely on deduction, use unconventional methods, and maintain a close relationship with a more grounded companion. House's surname also echoes Holmes's home, 221B Baker Street, through a series of character and setting references.

James Wilson corresponds in part to Dr. John Watson, Holmes's friend and narrative counterpart. The series also includes smaller references to Holmes, including House's apartment number and his use of a musical instrument.

House is not a direct adaptation of a Holmes story. Instead, the medical drama transfers the detective's mystery-solving structure into diagnosis, with symptoms replacing clues and diseases serving as the hidden culprit.