Aims: The study aimed to evaluate feasibility and safety of in-bag manual morcellation compared to uncontained power morcellation during laparoscopic myomectomy. Methods: A total of 72 women undergoing laparoscopic myomectomy were randomized into 2 treatment groups: 34 patients underwent in-bag manual morcellation (experimental group) and 38 were submitted to uncontained power morcellation (control group). The primary end point was the comparison of morcellation operative time (MOT). Total operative time (TOT), rate of intraoperative complication, and postoperative outcomes in the 2 groups were regarded as secondary outcomes. Results: Mean MOT and TOT were longer in the experimental group than in the control one (MOT: 9.47 ± 5.05 vs. 6.16 ± 7.73 min; p = 0.01; TOT: 113.24 ± 28.12 vs. 96.74 ± 33.51 min; p = 0.01). No intraoperative complications occurred in either group and no cases of bag disruption or laparotomic conversion were recorded. No significant difference in hemoglobin drop, hospital stay, and postoperative outcomes was reported between groups. Conclusion: In-bag manual morcellation appears a safe and feasible procedure and, despite slightly longer operative time, could represent an alternative to uncontained power morcellation.