Background & Aims Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors), commonly prescribed to prevent cardiovascular disease, promote apoptosis and limit proliferation of esophageal cancer cell lines. We investigated whether statin use after a diagnosis of esophageal cancer is associated with reduced esophageal cancer–specific and all-cause mortality. Methods We identified a cohort of 4445 men and women in the United Kingdom diagnosed with esophageal cancer from January 2000 through November 2009 using the General Practice Research Database. The National Cancer Registry and Office of National Statistics data sets established the histologic subtype and cancer-specific mortality, respectively. Cox proportional hazard regression analysis with time-dependent exposures estimated the association between statin use after diagnosis and esophageal cancer–specific and all-cause mortality. Results The median survival time of the entire cohort was 9.2 months (interquartile range IQR, 3.7–23.2 mo). Among subjects who used statins after a diagnosis of esophageal cancer, the median survival time was 14.9 months (IQR, 7.1–52.3 mo) compared with 8.1 months for nonusers (IQR, 3.3–20 mo). In the entire cohort, statin use after diagnosis was associated with a decreased risk of esophageal cancer–specific mortality (adjusted hazard ratio HR, 0.62; 95% confidence interval CI, 0.44–0.86) and all-cause mortality (HR, 0.67; 95% CI, 0.58–0.77). In patients with esophageal adenocarcinoma, statin use after diagnosis was associated with a decreased risk of esophageal cancer–specific mortality (HR, 0.61; 95% CI 0.38–0.96) and all-cause mortality (HR, 0.63; 95% 0.43–0.92). This effect was not observed in patients with esophageal squamous cell carcinoma. There was no evidence for effect modification of these associations with statin use before the cancer diagnosis. Conclusions In a large population-based cohort, statin use after a diagnosis of esophageal adenocarcinoma, but not esophageal squamous cell carcinoma, was associated with reduced esophageal cancer–specific and all-cause mortality.