Background: Taiwan has the highest prevalence of end-stage renal disease (ESRD) in the world. Patients with ESRD are considered to have high risks of influenza-related complications. Thus influenza vaccination is strongly recommended to reduce morbidity and mortality for this at-risk population. Objectives: The study aims to assess the effectiveness of influenza vaccination for elderly ESRD patients on the risk of mortality and hospitalization during the influenza season in Taiwan. Methods: This retrospective study included 27,615 ESRD patients aged 65 years or older extracted from the National Health Insurance Research Database, a nationally representative sample in Taiwan. Multivariate logistic regression analyses were used to compare the risk of mortality and hospitalization between vaccinated and unvaccinated group. Results: Approximately 37% elderly ESRD patients received influenza vaccine in 2011. After adjusting for confounders including age, gender, dialysis modality, income, urbanization, comorbid conditions, and health care utilization, the results showed that vaccinated group had a significantly lower all-cause mortality (relative risk [RR]: 0.72; 95% confidence interval [CI]: 0.64-0.82), hospitalization of respiratory diseases (RR: 0.78; 95% CI: 0i.71-0.86), pneumonia and influenza (RR: 0.81; 95% CI: 0.72-0.91), and heart disease (RR: 0.89; 95% CI: 0.81-0.99) when compared with unvaccinated group. Conclusion: This study suggested that influenza vaccination can reduce the risk of all-cause mortality and hospitalization of influenza-related complications during the influenza season among elderly ESRD patients in Taiwan.