Objective To systematically evaluate the clinical effectiveness and safety of raltitrexed plus cisplatin in the treatment of malignant pleural mesothelioma (MPM) when compared with other chemotherapy regimens. Methods We electronically searched PubMed, Embase, The Cochrane Library and Chinese Biomedicine Database to March, 2007. Randomized controlled trials (RCTs) and quasi-RCTs were identified, and Revman 4.2.10 was applied for statistical analyses. Results One RCT involving 250 patients was included, which compared raltitrexed plus cisplatin versus cisplatin alone in the treatment of MPM. In the intention-to-treat population, the median survival time was statistically longer in the raltitrexed plus cisplatin group as compared to cisplatin alone group. (11.4 versus 8.8 months, P=0.048). The incidence of grade 3/4 toxicities was similar between the two groups. Conclusion The current evidence available showed that, the combination of raltitrexed and cisplatin may prolong the survival time for MPM patients, with a low incidence of grade 3/4 toxicities. However, more high-quality RCTs are required to further define its clinical effectiveness.