The aim of the study is to compare outcomes of the patients who underwent HeartMate3 (HM3) implantation with conventional sternotomy (CS) and minimally invasive thoracotomy technique (MILT). From June 2013 to April 2019, 50 patients who underwent isolated HM3 implantation were included. Patients were divided into two groups according to the operative technique; of 50 patients, 28 were implanted with CS and 22 with MILT. All patients were evaluated for mortality, need of inotrope, blood product transfusion, intensive care unit stay, time on mechanical ventilation, and postoperative right ventricular failure. Primary outcomes were early mortality and occurrence of adverse events. Patients characteristics were similar; preoperative central venous pressure (CVP) and the ratio of CVP to pulmonary capillary wedge pressure (CVP/PCWP) were significantly higher in the MILT group versus the CS group (p < 0.05). Intensive care unit stay was significantly shorter in the MILT group (p < 0.05). Incidence of bleeding requiring exploratory sternotomy and postoperative drainage on the first postoperative day were statistically higher in the CS group (p < 0.05). Right ventricular failure was higher in the CS group but was not statistically significant (p = 0.4). There was no significant difference in long-term adverse events. The Kaplan-Meier survival analysis showed no difference between the groups (p = 0.66). The HM3 assist system can be successfully implanted with the MILT technique, which has proved to be safe and reproducible and yields good clinical outcomes.