To assess the prognostic impact of weight loss on clinical outcomes in patients with coronary artery disease (CAD). We performed a systematic review and meta-analysis of the prognostic effects of weight loss in patients with CAD on a composite outcome of all-cause mortality, cardiovascular mortality, and major adverse cardiac events considering studies published between January 1, 1964, and August 8, 2013. We considered weight loss "intentional" when it occurred in the presence of programmed therapeutic lifestyle changes and "observational" when no such intervention was specified. We searched 1218 abstracts, of which 12 studies with 14 cohorts met the inclusion criteria. A total of 35,335 patients (mean age, 64 years; 72% male; body mass index BMI, 30; 3.2 years of follow-up) were included. Overall, weight loss was associated with a greater risk of the composite outcome (relative risk RR, 1.30; 95% CI, 1.00-1.69; P=.05). However, heterogeneity was high (I(2)=90%) and was substantially explained by weight loss intentionality. Presumed intentional weight loss (4 cohorts) was associated with improved outcomes (RR, 0.67; 95% CI, 0.56-0.80; P<.001), whereas observational weight loss (10 cohorts) was associated with worsened outcomes (RR, 1.62; 95% CI, 1.26-2.08; P<.001; interaction P<.001). Whereas observational weight loss is associated with increased adverse cardiovascular events, intentional weight loss is associated with lower clinical events. These results suggest that the underlying mechanism of weight loss (ie, intentional or unintentional) affects its impact on subsequent risk in persons with known CAD.