CONTEXT.—: Patients with perforated appendicitis are often managed with antibiotic therapy followed by a delayed appendectomy. Histologic features of such specimens have been incompletely described, especially in the recent literature. OBJECTIVE.—: To describe the histomorphology of interval appendicitis with a focus on features that could mimic important conditions, such as infections, Crohn disease, and mucinous neoplasms. DESIGN.—: Histologic evaluation of 100 interval appendectomy specimens with clinical and radiologic correlation. RESULTS.—: A total of 54 of the 100 patients (54%) had radiologic evidence of appendiceal perforation, and 97% were treated with intravenous and/or oral antibiotic therapy prior to appendectomy. Percutaneous drains were placed in 34 cases (34%). Common histologic findings included mural eosinophilic infiltration (54%), periappendiceal fibrosis (54%), and xanthogranulomatous inflammation (31%). Periappendiceal fibrosis was frequent among patients with radiologic evidence of perforation. Nine cases (9%) featured pulse granulomata associated with fecal material. Epithelioid granulomata were detected in 6% of cases and were confined to mucosal lymphoid follicles in all cases. Only 4 of these were accompanied by mural lymphoid aggregates that raised the possibility of Crohn disease. Changes mimicking mucinous neoplasms were more common: 14% of cases (14 of 100) displayed goblet cell hyperplasia, 15% (15 of 100) contained diverticula, and 16% (16 of 100) showed mural or periappendiceal mucin pools. CONCLUSIONS.—: Although interval appendectomy specimens occasionally contain inflammatory infiltrates that mimic infections and/or Crohn disease, changes that can be confused with mucinous neoplasms are more frequently encountered.