Background/Objective: Chitosan is increasingly being used in the United States as an over-the-counter cholesterol-lowering agent. The positively charged amino groups of chitosan may have the ability to bind negatively charged molecules such as lipids and bile acids, inducing a greater fractional excretion in the feces. To better characterize the impact of chitosan on serum lipids in hypercholesterolemic patients, we performed a meta-analysis of randomized controlled trials. Methods: A systematic literature search of Medline, Embase, Cochrane Central and the Natural Medicines Comprehensive Database was conducted from the earliest possible date through May 2008. Trials were included in the analysis if they were randomized, placebo-controlled trials of chitosan in hypercholesterolemic patients and reported efficacy data on total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol or triglycerides. The weighted mean difference (WMD) of the change from baseline (in milligrams per deciliter) with 95% confidence interval was calculated as the difference between the mean in the chitosan and placebo groups using a random-effects model. Results: Six studies (n = 416 patients) met the inclusion criteria. Upon meta-analysis, the use of chitosan significantly lowered total cholesterol [WMD, –11.59 mg/dl (–21.45 to –1.73), p = 0.02] but not LDL cholesterol, HDL cholesterol or triglycerides. Conclusions: Based upon the currently available literature, we can only say that chitosan beneficially affects total cholesterol with 95% confidence. Additional, larger randomized controlled trials are needed to better characterize the effect of chitosan on other lipoproteins.