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BACKGROUND: Diverticular disease is a common condition that increases in prevalence with age. Recent theories on the pathogenesis of diverticular inflammation have implicated chronic inflammation similar to that seen in ulcerative colitis. Mesalamine, or 5‐aminosalicylic acid (5‐ASA), is a mainstay of therapy for individuals with ulcerative colitis. Accordingly, 5‐ASA has been studied for prevention of recurrent diverticulitis. OBJECTIVES: To evaluate the efficacy of mesalamine (5‐ASA) for prevention of recurrent diverticulitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8), in the Cochrane Library; Ovid MEDLINE (from 1950 to 9 September 2017); Ovid Embase (from 1974 to 9 September 2017); and two clinical trials registries for ongoing trials ‐ Clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform database (9 September 2017). We also searched proceedings from major gastrointestinal conferences ‐ Digestive Disease Week (DDW), United European Gastroenterology Week (UEGW), and the American College of Gastroenterology (ACG) Annual Scientific Meeting ‐ from 2010 to September 2017. In addition, we scanned reference lists from eligible publications, and we contacted corresponding authors to ask about additional trials. SELECTION CRITERIA: We included randomised controlled clinical trials comparing the efficacy of 5‐ASA versus placebo or another active drug for prevention of recurrent diverticulitis. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as defined by Cochrane. Three review authors assessed eligibility for inclusion. Two review authors selected studies, extracted data, and assessed methodological quality independently. We calculated risk ratios (RRs) for prevention of diverticulitis recurrence using an intention‐to‐treat principle and random‐effects models. We assessed heterogeneity using criteria for Chi(2) (P < 0.10) and I(2) tests (> 50%). To explore sources of heterogeneity, we conducted a priori subgroup analyses. To assess the robustness of our results, we carried out sensitivity analyses using different summary statistics (RR vs odds ratio (OR)) and meta‐analytical models (fixed‐effect vs random‐effects). MAIN RESULTS: We included in this review seven studies with a total of 1805 participants. We judged all seven studies to have unclear or high risk of bias. Investigators found no evidence of an effect when comparing 5‐ASA versus control for prevention of recurrent diverticulitis (31.3% vs 29.8%; RR 0.69, 95% confidence interval (CI) 0.43 to 1.09); very low quality of evidence). Five of the seven studies provided data on adverse events of 5‐ASA therapy. The most commonly reported side effects were gastrointestinal symptoms (epigastric pain, nausea, and diarrhoea). No significant difference was seen between 5‐ASA and control (67.8% vs 64.6%; RR 0.98, 95% CI 0.91 to 1.06; P = 0.63; moderate quality of evidence), nor was significant heterogeneity observed (I(2) = 0%; P = 0.50). AUTHORS' CONCLUSIONS: The effects of 5‐ASA on recurrence of diverticulitis are uncertain owing to the small number of heterogenous trials included in this review. Rates of recurrent diverticulitis were similar among participants using 5‐ASA and control participants. Effective medical strategies for prevention of recurrent diverticulitis are needed, and further randomised, double‐blinded, placebo‐controlled trials of rigorous design are warranted to specify the effects of 5‐ASA (mesalamine) in the management of diverticulitis.