Objective: This study aimed to investigate the potential determining epidemiological and clinical risk factors affecting the survival of esophageal cancer (EC) patients across multiple hospitals in China. Methods: This was a multicenter study comprising of newly diagnosed EC cases from Beijing, Hebei, Henan, Hubei, Zhejiang, and Guangdong Province of China. Their baseline characteristics and treatment methods data were collected from their medical records. The EpiData software was used for data quality control. The Kaplan-Meier method was used to estimate their overall survival (OS), and the Cox's proportional hazard regression model was used to estimate hazard ratios (HR) and 95% confidence interval (CI). Results: The 3- and 5-year OS rates of the 5283 investigated EC patients were 49.98% and 39.07%, respectively. Their median survival was 36.00 months. The median survival time of females was longer than that of males (females vs. males: 45.00 vs. 33.00, P < 0.001). The 5-year OS rate of patients who never-smoked was higher than that of smokers (never-smokers vs smokers: 40.73% vs. 37.84%, P = 0.001). There was no significant difference in the 5-year OS rate between drinkers and never-drinkers (drinkers vs never-drinkers: 34.22% vs. 29.65%, P = 0.330). In multivariate analysis, pathological stage (stage II: HR = 1.80, 95% CI = 1.40-2.31; stage III: HR = 2.62, 95% CI = 2.06-3.34; stage IV: HR = 3.90, 95% CI = 2.98-5.09), poor differentiation/undifferentiated (HR = 1.34, 95% CI = 1.11-1.63), not married status (HR = 2.45, 95% CI = 1.49-4.04), production and service personnel (HR = 1.36, 95% CI = 1.01-1.83) and farming/fishing (HR = 1.40, 95% CI = 1.12-1.76) were independent prognostic risk factors for poor EC survival. Tumors in the thoracic or abdominal part of the esophagus, female and family history of any cancer were independent factors predictive of a good EC OS. Conclusion: Gender, marital status, occupation, family history of any cancer, tumor topographical site, differentiation status, and pathological stage were associated with the survival rate of EC. This study reveals important clinical characteristics of esophageal cancer patients in China and provides helpful information for their clinical management and surveillance. © 2020 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center