Background: Laparoscopic cholecystectomy is one of the most common surgeries performed nowadays. There are lot of advances in closure of cystic duct and artery (clip ligation, suture ligation), but it remains an enigma regarding efficacy, safety and postoperative complications for using non-absorbable suture material or Liga clip for the operating surgeon in laparoscopic cholecystectomy. Objectives: Our study aimed to evaluate the efficacy, safety and complications of non-absorbable sutures ligation versus clips application in laparoscopic cholecystectomy, and to compare the operative time and cost effectiveness of the two surgical approaches in laparoscopic cholecystectomy. Methods: This prospective study was performed between August 2014 and February 2015 in M. M. Institute of Medical Science and Research, in a rural center, Mullana, India. The study included 160 patients who were diagnosed with chronic cholecystitis in a single unit. Subjects were divided into two groups and all cases were operated by a single surgeon. The cystic pedicle was tied with non-absorbable material (silk 2-0) in group A and with Titanium clips using a clip applicator in group B. Results: The application of silk and clips for cystic duct and artery ligation in laparoscopic cholecystectomy can be safely used. The mean time for ligation of cystic duct was 2.50 (SD ±0.25) in group A and 1.50 min (SD ±1.85) in group B, with P<0.001, which was significant. Similarly, the mean time for ligation of cystic artery was 1.50 min (SD±0.20) in group A and 1.36 min (SD ±0.11) in group B, with P>0.001. There were no postoperative complications, such as wound infection or bile leakage, in any of the two methods. The cost of material for silk suture (40-60 Rupees or 0.62-0.92 $) is definitely much lower than that for Liga clips (790-1000 Rupees or 12.28-15.55 $). For the use of clips, a clip applicator is required, but in case of silk ligation no special instrument is required and silk is also easily available. Conclusion: In laparoscopic cholecystectomy, ligation of cystic duct and cystic artery with clips takes less time than by silk suture. We conclude that both ligation techniques can be safely and effectively used. Training for junior surgeons is necessary to avoid potential complications.