In native mitral valve infective endocarditis (NMVIE), the respective values of mitral valve repair (MVR) and mitral valve replacement (MVRP) are still debated. We compared MVR and MVRP in a large prospective series of pts operated on for NMVIE in La Timone Hospital, Marseille. Between 2010 and 2017, 151 pts with NMVIE underwent early (< 30 days) surgery. Among them, 115 (76%) underwent MVR, and 36 (24%) MVRP. Clinical and outcome features were compared between the 2 groups. A composite primary endpoint included death, need for reoperation, and recurrence during a 6-month FU. In-hospital and 6-month mortality were part of secondary end-points. As compared with MVR, MVRP pts had more associated aortic abscess (15 vs 4%, P = 0.03), and more restrictive lesions (28 vs 3%, P < 0.001). Thirty-nine (26%) pts underwent urgent surgery (during the 1st week). The primary end-point occurred in 23 (20%) pts. Main factors associated with bad outcome were renal failure ( P = 0.002), cerebral embolism ( P < 0.01), aortic abscess ( P < 0.001), and MVRP ( P = 0.001), while MVR was protective ( P = 0.001). By multivariate analysis, factors associated with bad outcome were cerebral embolism (HR = 3.46, P < 0.001) and heart failure (HR = 2.25, P = 0.04), while only MVR was protective (HR = 0.36, P = 0.003). Death occurred in-hospital in 8 (5%) pts and during the 6-month FU in 16 (11%) pts. MVR was associated with lower in-hospital and long-term mortality (HR = 0.11, CI 0.02–0.45, P = 0.002, and HR = 0.22, CI 0.08–0.58, P = 0.002, respectively). Timing of surgery had no influence on prognosis, while commissural lesions were paradoxically associated with better outcome ( P = 0.02). Early MVR for NMVIE is associated with better outcome than MVRP, without excess reoperation rate, residual mitral regurgitation, or recurrence. In experienced hands, early MVR is technically feasible in 76% of NMVIE and should be the preferred option in these pts.