BACKGROUND: Consumption of nuts has been associated with a decreased risk of cardiovascular disease events and death. Walnuts in particular have a unique profile: they are rich in polyunsaturated fatty acids, which may improve blood lipids and other cardiovascular disease risk factors. OBJECTIVES: We aimed to conduct a literature review and a meta-analysis to combine the results from several trials and to estimate the effect of walnuts on blood lipids. DESIGN: Literature databases were searched for published trials that compared a specifically walnut-enhanced diet with a control diet. We conducted a random-effects meta-analysis of weighted mean differences (WMDs) of lipid outcomes. RESULTS: Thirteen studies representing 365 participants were included in the analysis. Diets lasted 4-24 wk with walnuts providing 10-24% of total calories. When compared with control diets, diets supplemented with walnuts resulted in a significantly greater decrease in total cholesterol and in LDL-cholesterol concentrations (total cholesterol: WMD = -10.3 mg/dL, P < 0.001; LDL cholesterol: WMD = -9.2 mg/dL, P < 0.001). HDL cholesterol and triglycerides were not significantly affected by walnut diets more than with control diets (HDL cholesterol: WMD = -0.2, P = 0.8; triglycerides: WMD = -3.9, P = 0.3). Other results reported in the trials indicated that walnuts provided significant benefits for certain antioxidant capacity and inflammatory markers and had no adverse effects on body weight [body mass index (kg/m(2)): WMD = -0.4, P = 0.5; weight (kg): WMD = -0.05, P = 0.97]. CONCLUSIONS: Overall, high-walnut-enriched diets significantly decreased total and LDL cholesterol for the duration of the short-term trials. Larger and longer-term trials are needed to address the effects of walnut consumption on cardiovascular risk and body weight.