BACKGROUND 5-Aminosalicylates are the standard treatment for induction and maintenance of remission in mild-to-moderate ulcerative colitis. In recent years, the 5-aminosalicylic acid-containing pro-drug balsalazide has been the focus of attention. OBJECTIVE To compare the efficacy and tolerance of balsalazide and mesalazine by meta-analysis. METHODS Pubmed, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for studies comparing the efficacy and/or tolerance of balsalazide with mesalazine in the management of UC. The search terms were: "mesalazine" or "5-aminosalicylic acid" and "balsalazide" and "ulcerative colitis." Data were collected from 1966 to 2007 (up to February). There was no language restriction. "Symptomatic remission," "complete remission," "relapse rate," "total adverse events," and "withdrawals because of adverse events" were the key outcomes of interest. RESULTS Six randomized placebo-controlled clinical trials met our criteria and were included in the meta-analysis. In these "symptomatic remission," "complete remission," "relapse rate," "total adverse events," and "withdrawals because of adverse events" were evaluated in three, three, two, five, and six of the trials, respectively. They included 653 patients consisting of 55.4% men and 44.6% women randomized to receive either balsalazide or mesalazine. Pooling of three trials for symptomatic remission yielded a significant relative risk (RR) of 1.23 (95% confidence interval of 1.03-1.47, P = 0.02). The summary RR for complete remission in three trials was 1.3 (95% CI of 1.002-1.68, P = 0.048). Pooling of two trials for the outcome of relapse yielded a non-significant RR of 0.77 (95% CI of 0.56-1.07, P = 0.12). Pooling five studies from which data for any adverse events were extracted, yielded a non-significant RR of 0.87 (95% CI of 0.75-1.001, P = 0.53). The summary RR for withdrawals because of adverse events in six trials was 0.69, a non-significant RR (95% CI of 0.37-1.29, P = 0.24). CONCLUSIONS Balsalazide is more effective than mesalazine in induction of remission, but balsalazide has no benefit compared with mesalazine in preventing relapse in the population selected. The number of patients with any adverse events and withdrawals because of severe adverse events is similar for mesalazine and balsalazide.