Studies on the clinical efficacy of influenza vaccination on patients with systemic lupus erythematosus (SLE) are scant. The present study compared the incidence of hospitalization, morbidity, and mortality in patients with SLE between cohorts with and without influenza vaccination. We used the Taiwan's insurance claims data between 2001 and 2012 for identifying annual adult patients with SLE with (N = 1765) and without (N = 8360) influenza vaccination. The incidence rate ratio and hazard ratio (HR) for morbidities and mortality were measured for the vaccine and nonvaccine cohorts. The vaccine cohort had a lower hospitalization rate than did the nonvaccine cohort, with an adjusted HR of 0.82 (95% CI 0.73-0.92). Furthermore, the vaccine cohort was less likely to be admitted to the intensive care unit [adjusted HR 0.55 (95% CI 0.39-0.79)], to be hospitalized for septicemia, bacteremia, or viremia [adjusted HR 0.48 (95% CI 0.32-0.73)], to undergo in-hospital dialysis [adjusted HR 0.40 (95% CI 0.20-0.81)], and were less predisposed to death [adjusted HR 0.41 (95% CI 0.27-0.61)]. In conclusion, influenza vaccination in patients with SLE is associated with a reduced risk of morbidity and mortality.