CONTEXT: Although a recent meta-analysis of randomized controlled trials showed that adoption of a vegetarian diet reduces plasma lipids, the association between vegetarian diets and long-term effects on plasma lipids has not been subjected to meta-analysis. OBJECTIVE: The aim was to conduct a systematic review and meta-analysis of observational studies and clinical trials that have examined associations between plant-based diets and plasma lipids. DATA SOURCES: MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for articles published in English until June 2015. STUDY SELECTION: The literature was searched for controlled trials and observational studies that investigated the effects of at least 4 weeks of a vegetarian diet on plasma lipids. DATA EXTRACTION: Two reviewers independently extracted the study methodology and sample size, the baseline characteristics of the study population, and the concentrations and variance measures of plasma lipids. Mean differences in concentrations of plasma lipids between vegetarian and comparison diet groups were calculated. Data were pooled using a random-effects model. RESULTS: Of the 8385 studies identified, 30 observational studies and 19 clinical trials met the inclusion criteria (N = 1484; mean age, 48.6 years). Consumption of vegetarian diets was associated with lower mean concentrations of total cholesterol (-29.2 and -12.5 mg/dL, P < 0.001), low-density lipoprotein cholesterol (-22.9 and -12.2 mg/dL, P < 0.001), and high-density lipoprotein cholesterol (-3.6 and -3.4 mg/dL, P < 0.001), compared with consumption of omnivorous diets in observational studies and clinical trials, respectively. Triglyceride differences were -6.5 (P = 0.092) in observational studies and 5.8 mg/dL (P = 0.090) in intervention trials. CONCLUSIONS: Plant-based diets are associated with decreased total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, but not with decreased triglycerides. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number CRD42015023783. Available at: https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015023783.