Background Most previous studies dealing with predictors of surgical outcome in prosthetic valve endocarditis included patients with aortic and/or mitral valve prostheses. Here, we concentrate on isolated prosthetic mitral endocarditis due to heterogeneity of epidemiological data, anatomical factors, and surgical techniques between mitral, prosthetic mitral, and aortic endocarditis between prosthetic mitral and prosthetic aortic endocarditis. Methods Data of 40 patients reoperated upon due to isolated prosthetic mitral endocarditis between July 2015 and March 2017 were retrospectively collected and analyzed. Results Independent predictors of major postoperative complications on multivariate analysis were: no blood cultures before referral (odds ratio 6.36, 95% confidence interval: 1.44-28.15), inadequate response to medical treatment (odds ratio 11.38, 95% confidence interval: 1.29-100.25), and serum creatinine ≥2.0 mg·dL (odds ratio 4.56, 95% confidence interval: 1.07-19.36). Independent predictors of hospital mortality were: congestive heart failure (odds ratio 30.91, 95% confidence interval: 2.02 to 473.87), embolization (odds ratio 18.24, 95% confidence interval:1.94-171.91), peri-annular extension of infection (odds ratio 12.68, 95% confidence interval: 1.30-123.43), serum creatinine on admission > 2 mg·dL (odds ratio 9.67, 95% confidence interval: 1.97-47.48), and early prosthetic valve endocarditis (odds ratio 7.80, 95% confidence interval: 1.35-45.00). EuroSCORE II > 5.93% was associated with the highest predictive value for hospital mortality (area under the curve 0.813). Conclusion Certain factors can predict morbidity and mortality in surgery for isolated mitral prosthetic valve endocarditis. EuroSCORE II has a good ability to predict hospital mortality in surgery for mitral prosthetic valve endocarditis.