Background and Objectives: Transaxillary access is a straightforward “single incision—direct vision” concept, based on a 5 cm skin incision in the right anterior axillary line. It is suitable for aortic, mitral and tricuspid surgery. The present study evaluates the hospital outcomes of the transaxillary access for isolated mitral valve surgery compared with full sternotomy. Patients and Methods: The final study group included 480 patients. A total of 160 consecutive transaxillary patients served as treatment group (MICS-MITRAL). Based on a multivariate logistic regression model including age, sex, body-mass-index, EuroScore II and LVEF, a 1:2 propensity matched control-group (n = 320) was generated out of 980 consecutive sternotomy patients. Redo surgeries, endocarditis or combined procedures were excluded. The mean age was 66.6 ± 10.6 years, 48.6% (n = 234) were female. EuroSCORE II averaged 1.98 ± 1.4%. Results: MICS-MITRAL had longer perfusion (88.7 ± 26.6 min vs. 68.7 ± 32.7 min; p < 0.01) and cross-clamp (64.4 ± 22.3 min vs. 49.7 ± 22.4 min; p < 0.01) times. This did not translate into longer procedure times (132 ± 31 min vs. 131 ± 46 min; p = 0.76). Both groups showed low rates of failed repair (MICS-MITRAL: n = 6/160; 3.75%; Sternotomy: n = 10/320; 3.1%; p = 0.31). MICS-MITRAL had lower transfusion rates (p ≤ 0.001), less re-exploration for bleeding (p = 0.04), shorter ventilation times (p = 0.02), shorter ICU-stay (p = 0.05), less postoperative hemofiltration (p < 0.01) compared to sternotomy patients. No difference was seen in the incidence of stroke (p = 0.47) and postoperative delirium (p = 0.89). Hospital mortality was significantly lower in MICS-MITRAL patients (0.0% vs. 3.4%; p = 0.02). Conclusions: The transaxillary access for MICS-MITRAL provides superior cosmetics and excellent clinical outcomes. It can be performed at least as safely and in the same time frame as conventional mitral surgery by sternotomy.