Objectives: Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. Evidence for treatment with 5-aminosalicylic acid (5-ASA) drugs is conflicting. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine this issue. Methods: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through December 2010). Authors of studies were contacted to provide additional information on trials where required, and experts in the field were contacted to identify unpublished studies. Eligible trials recruited adults with active or quiescent CD and compared 5-ASAs with placebo, or no treatment. Dichotomous data were pooled to obtain relative risk (RR) of failure to achieve remission in active CD, and RR of relapse of disease activity in quiescent CD, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. Results: The search identified 3,061 citations. Twenty-two RCTs were eligible. Six RCTs compared 5-ASA with placebo in active CD remission. There was a trend towards a benefit with sulfasalazine over placebo (two RCTs, RR of failure to achieve remission=0.83; 95% CI=0.69–1.00), but no definite benefit of mesalamine over placebo (four RCTs, RR=0.91; 95% CI=0.77–1.06). Neither sulfasalazine nor mesalamine were effective in preventing quiescent CD relapse, but in a per protocol analysis mesalamine appeared to reduce risk of relapse (RR=0.79; 95% CI=0.66–0.95, NNT=13). Conclusions: The role of 5-ASAs in inducing remission of active CD and preventing relapse of quiescent CD remains uncertain, and more RCTs are required.