Objective To assess the efficacy and safety of mesalazine versus sulfasalazine in the treatment of ulcerative colitis.Methods The literatures were searched from PubMed (1966 to January 2010), the Cochrane Library (1966 to January 2010), EMbase (1974 to January 2010), CNKI (1994 to January 2010), VIP (1989 to January 2010), and CBM (1978 to January 2010). The data were extracted, the quality of studies was evaluated according to The Cochrane Handbook, and meta-analyses were performed using RevMan 5.0 software. Results Sixteen RCTs involving 1 333 patients were included in this study. The results of meta-analyses showed that the total effective rate of the mesalazine group was significantly higher than that of the sulfasalazine group (RR=1.10, 95%CI 1.04 to 1.17, Plt;0.05), and significant differences were noted in the total remission rate (RR=1.82, 95%CI 1.14 to 2.91, Plt;0.05), while there was no significant difference in the relapse rate between the two groups (RR=0.86, 95%CI 0.57 to 1.29, Pgt;0.05). Twelve RCTs reported adverse effects and meta-analyses showed that the incidence of adverse effects was significantly lower in the mesalazine group than in the sulfasalazine group (RR=0.56, 95%CI 0.42 to 0.73, Plt;0.05). Conclusion Analyses show that mesalazine is much more effective and safe in the management of ulcerative colitis than sulfasalazine. However, there is a moderate risk of bias due to methodological quality problems in all 16 included RCTs, so more strictly-designed multi-centered randomized controlled trials with high quality in large-scale are needed to confirm this result.