PURPOSE: Preclinical studies have shown that statins reduce proliferation in esophageal cancer. Three recent observational studies have shown encouraging results but suffered from limitations. This work aimed to assess at the Belgian population level whether statin usage was associated with a decreased mortality in esophageal cancer patients. METHODS: We conducted an observational, population-based study by linking data of the Belgian Cancer Registry (BCR) with medical claims data coming from health insurance companies and mortality records collected by regional governments for patients diagnosed with esophageal cancer between 2004 and 2014. Using time-dependent Cox regression models, hazard ratios (HRs) and 95% confidence intervals (CI) for overall and cancer-specific mortality were calculated. RESULTS: Of 6,238 patients with stage I-III esophageal cancer, post-diagnostic use of statins was found in 1,628 (26%) patients. Statins use after diagnosis was associated with a reduction in overall mortality (adjusted HR = 0.84, 95% CI [0.77; 0.92]) and cancer-specific mortality (adjusted HR = 0.87, 95% CI [0.78; 0.97]). Similar association were also seen for pre-diagnostic statin use in overall (adjusted HR = 0.83, 95% CI [0.76-0.91]) and cancer-specific analysis (adjusted HR = 0.86, 95% CI [0.77-0.96]). CONCLUSIONS: In this large cohort of Belgian patients with esophageal cancer, statins use after diagnosis was associated with a decreased mortality.