Objectives To assess the efficacy and safety of cytidine diphosphate choline for patients with acute stroke. Methods Such databases as PubMed, The Cochrane Library, EMbase, Web of Science, CNKI, VIP Database and Chinese Medical Association Journals were searched from the establishment to September of 2010, and the references of the included literatures were also searched to collect randomized controlled trials (RCTs) of cytidine diphosphate choline for patients with acute stroke. The data were extracted by two reviewers independently in accordance with the inclusion criteria. The quality of included trials was evaluated according to the Jadad scale standard. RevMan5.0 software was used for data analyses. Results Thirteen RCTs involving 2837 patients were included. The results of meta-analyses showed that, there was no significant difference in the mortality or the rate of dependency at the end of follow-up (OR=0.94, 95%CI 0.66 to 1.36, P=0.75) between the cytidine diphosphate choline group and the placebo group. But the total effective rate of the cytidine diphosphate choline group was higher than that of the placebo group with a significant difference (OR=1.72, 95%CI 1.41 to 2.10, Plt;0.000 01). Five trials reported the incidence of adverse reaction of cytidine diphosphate choline treatment which showed the adverse reaction was mild; no severe adverse events (SAEs) were reported and the clinical application was safe. Conclusion The cytidine diphosphate choline is effective and safe for acute stroke. However, it is invalid to reduce the mortality and the rate of dependency at the end of three months’ follow-up.