Context: Hysterectomy is the most commonly performed gynecological procedure around the world. Hemostasis is of major concern in an enlarged uterus as chances of hemorrhage are more. New laparoscopic vessel sealing devices have been developed for laparoscopic tissue dissection and vessel sealing. In this study, an ALAN vessel sealer, an indigenous electrothermal bipolar vessel sealing device, is compared with ENSEAL device with respect to safety, efficacy, and perioperative outcomes in laparoscopic hysterectomy for a large uterus. Aims and objectives: This study aimed to determine the efficacy and safety of electrothermal bipolar vessel sealer (ALAN vessel sealer) vs ENSEAL in total laparoscopic hysterectomy (TLH) for a large uterus. Materials and methods: This prospective randomized case–control study included 100 women who underwent TLH for a large fibroid uterus. Of them, 50 women underwent TLH using ALAN vessel sealer, and the remaining 50 using ENSEAL. Efficacy, safety, and perioperative outcomes of both the groups were compared. Statistical analysis: Statistical analysis was done using SPSS version 16.0 software. For evaluating continuous variables and discrete variables, independent T-tests, and Chi-square tests, respectively, were used. Results: Duration of surgery in ALAN vessel sealer group was 56.90 ± 12.45 minutes and in ENSEAL group was 57.25 ± 13.54 minutes (p = 0.9) and mean blood loss in group A and group B was 111.40 ± 22.32 and 107.84 ± 20.33 mL, respectively ( p = 0.4), both of the data were not statistically significant. No significant differences were noticed in the demographic characteristics, intraoperative, and postoperative complications between the two groups. Conclusions: The ALAN vessel sealer is safe and as efficient as ENSEAL in decreasing blood loss and operative time when laparoscopic hysterectomy is performed for an enlarged uterus. It is cost-effective and a promising instrument for TLH in developing countries.