Background. The aim of the study was to assess the primary efficacy of robot-assisted microwave ablation and compare it to manually guided microwave ablation for percutaneous ablation of aver malignancies. Patients and methods. We performed a retrospective single center evaluation of microwave ablations of 368 liver tumors in 192 patients (36 female, 156 male, mean age 63 years). One hundred and nineteen ablations were performed between 08/2011 and 03/2014 with manual guidance, whereas 249 ablations were performed between 04/2014 and 11/2018 using robotic guidance. A 6-week follow-up (ultrasound, computed tomography and magnetic resonance imaging) was performed on all patients. Results. The primary technique efficacy outcome of the group treated by robotic guidance was significantly higher than that of the manually guided group (88% vs. 76%; p = 0.013). Multiple logistic regression analysis indicated that a small tumor size (<= 3 cm) and robotic guidance were significant favorable prognostic factors for complete ablation. Conclusions. In addition to a small tumor size, robotic navigation was a major positive prognostic factor for primary technique efficacy.