BACKGROUND The objective was to compare long-term survival after operations for active infective endocarditis (IE) in native or prosthetic valves. We also investigated differences in early death and postoperative complications. METHODS We conducted a population-based cohort study including all patients who underwent operations for IE between January 2002 and July 2012. The SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry and patients records were used to acquire information about patient characteristics, preoperative comorbidities, and postoperative complications. Date of death was ascertained by using the Swedish personal identity number and the Total Population Register at Statistics Sweden. We used multivariable Cox regression to analyze the association between prosthetic valve IE and survival. RESULTS Of the 252 included patients, 22% underwent operations for prosthetic valve IE. There was no significant difference in unadjusted 5-year survival between patients who underwent operations for prosthetic valve IE compared with native valve IE (75% vs 65%; p = 0.34). We found no significant association between operations for prosthetic valve IE and death (multivariable adjusted hazard ratio, 0.83; 95% confidence interval, 0.46 to 1.49) compared with native valve IE. There was no significant difference in 30-day mortality between prosthetic and native valve IE (14% vs 12%; p = 0.61), with a multivariable adjusted odds ratio of 0.62 (95% confidence interval, 0.24 to 1.64). CONCLUSIONS We found no significant difference in long-term survival between patients who underwent operations for prosthetic valve IE compared with native valve IE. Early death and morbidity were also similar between the groups. These results are promising because an increasing amount of patients with IE have prosthetic valve infections.