Objectives/Hypothesis: Mastoidectomy has long been identified as an effective method of treatment for chronic ear infection. The effect of mastoidectomy on patients without evidence of active infectious disease remains highly debated and unproven. The objective in the study was to examine the impact of mastoidectomy on the repair of uncomplicated tympanic membrane perforations. Study Design: Retrospective study of patients at tertiary referral center. Methods: Four hundred eighty-four patients who underwent surgical repair of simple tympanic membrane perforations were identified and reviewed in a retrospective manner. Simple tympanic membrane perforations were defined as tympanic membrane perforations of any size and location without any of the following confounding variables: 1) active infection (active otorrhea, abnormal middle ear mucosa, or granulations tissue); 2) ossicular abnormalities (ossicular fixation, ossicular discontinuity, ossicular malformation, or ossicular absence); 3) cholesteatoma; or 4) prior attempt at tympanic membrane repair (prior tympanoplasty or mastoidectomy). Surgical outcome and clinical course were assessed to compare results of tympanic membrane perforation repair with and without canal wall up mastoidectomy. Results: Tympanic membrane repair was equally effective in both groups at 91%. Hearing results were comparable. Development of persistent ipsilateral otological disease requiring a subsequent ipsilateral procedure was approximately twice as common in the tympanoplasty group. In the tympanoplasty group, 14.1% of patients underwent subsequent ipsilateral otological procedures, and 6.1% of patients in the tympanoplasty with mastoidectomy intact canal wall group underwent subsequent ipsilateral procedures (P < .05). The most common subsequent ipsilateral procedures were tympanoplasty, tympanostomy tube placement, tympanoplasty with mastoidectomy canal wall up, and tympanoplasty with mastoidectomy canal wall down, in that order. After including untreated tympanic membrane perforations as subsequent procedures, the adjusted rate of subsequent procedures was 15.5% in the tympanoplasty group and 12.2% in the tympanoplasty with mastoidectomy group (P > .05). Conclusion: Mastoidectomy was not necessary for successful repair of simple tympanic membrane perforations. However, mastoidectomy impacted the clinical course in patients by reducing the number of patients requiring future procedures and by decreasing disease progression. This suggests that even in the absence of active evidence of infection, mastoidectomy improved the underlying disease process. Combining mastoidectomy with tympanoplasty during repair of simple perforations in patients with no active evidence of infection remains an appropriate option and may be valuable in reducing the need for future surgery.