The purpose of this ongoing prospective study is to evaluate the feasibility, safety, and efficacy of a total laparoscopic approach for ultrasound-guided cryoablation of primary and secondary hepatic tumors. Of 56 patients who underwent ultrasound-guided cryoablation, a total laparoscopic approach was employed in 18 (5 men, 13 women; mean age 48.6 years, range 35-77 years). Fifteen patients were included for secondary hepatic tumors and three for primary hepatic tumors. Selection criteria were the presence of three or fewer nodules, less than 40% liver volume replaced by tumor, and absence of extrahepatic disease. Altogether 28 lesions were confirmed by intraoperative laparoscopic ultrasonography and were treated; 25 by ultrasound-guided laparoscopic cryoablation and 3 by laparoscopic wedge resection. After cryoablation, surface parenchymal splits with bleeding from the frozen tissue were observed in six patients and required conversion to open surgery in two patients whose lesions were located in segment 8. No major complication and no mortality were observed. One or more minor complications occurred in nine patients; they included pleural effusion (n = 8, 44.4%), subdiaphragmatic fluid collection ( n = 3, 16.6%), worsening hepatic insufficiency in a cirrhotic patient (n = 1, 5.5%), and wound infection in a patient converted to open surgery (n = 1, 5.5%). The mean hospital stay was 6.4 days (range 3-14 days). At a mean follow-up of 10.8 months (range 5-16 months) all patients are alive and 14 are disease-free, as demonstrated by normalization of tumor markers and negative magnetic resonance imaging. In carefully selected patients total laparoscopic ultrasound-guided cryoablation is feasible and safe. A longer period of follow-up is required to evaluate the efficacy of the procedure and its impact on survival.