Although infliximab and immunosuppressives have both proved to be effective in the treatment of Crohn's disease (CD), the efficacy and safety of the combination therapy remained undetermined yet. We performed a meta-analysis to evaluate the efficacy and safety of combination therapy of infliximab and immunosuppressives compared with monotherapy for maintaining steroid-free clinical remission on patients with CD. We searched PubMed, Cochrane Library, and EMBASE. The primary end point was steroid-free clinical remission after induction infusion and in short-term and long-term follow-ups. Total adverse events, severe adverse event, infection, severe infection, infusion reaction, sepsis, tuberculosis, and malignancy also were analyzed. Meta-analysis was carried out by combining the odds ratio (OR) between the combination therapy and monotherapy of the individual studies in a global OR, with statistical heterogeneity tested using the χ²-test and the I²-test. Five studies with eight comparisons involving 1026 patients were included. In an overall analysis, combination therapy was more effective than monotherapy for induction of remission at weeks 10-12 [mean OR=2.50; 95% confidence interval (CI)=1.46-4.30; P=0.0009)] and maintenance of remission at weeks 24-26 (mean OR=2.32; 95% CI=1.75-3.08; P<0.00001) and weeks 48-54 (mean OR=1.83; 95% CI=1.44-2.32; P<0.00001). In all five studies, combination therapy did not increase the risk of total adverse event, severe adverse event, infection, severe infection, and infusion reaction. The combination therapy of infliximab and immunosuppressives was more effective than monotherapy in the induction and maintenance remission of CD, and adverse events did not increase. However, larger clinical trials with longer follow-up are warranted to further assess the efficacy and safety profile of combination therapy.