Coffee consumption has been inconsistently associated with risk of stroke. The authors conducted a meta-analysis of prospective studies to quantitatively assess the association between coffee consumption and stroke risk. Pertinent studies were identified by searching PubMed and Embase from January 1966 through May 2011 and by reviewing the reference lists of retrieved articles. Prospective studies in which investigators reported relative risks of stroke for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Eleven prospective studies, with 10,003 cases of stroke and 479,689 participants, met the inclusion criteria. There was some evidence of a nonlinear association between coffee consumption and risk of stroke (P for nonlinearity = 0.005). Compared with no coffee consumption, the relative risks of stroke were 0.86 (95% confidence interval (95% CI): 0.78, 0.94) for 2 cups of coffee per day, 0.83 (95% CI: 0.74, 0.92) for 3-4 cups/day, 0.87 (95% CI: 0.77, 0.97) for 6 cups/day, and 0.93 (95% CI: 0.79, 1.08) for 8 cups/day. There was marginal between-study heterogeneity among study-specific trends (I₂ = 12% and I₂ = 20% for the first and second spline transformations, respectively). Findings from this meta-analysis indicate that moderate coffee consumption may be weakly inversely associated with risk of stroke.