AIMTo study the effect of different techniques of cystic duct closure on bile leakage after laparoscopic cholecystectomy (LC) for biliary disease.METHODSA systematic search of MEDLINE, Cochrane and EMBASE was performed. Rate of cystic duct leakage (CDL) was the primary outcome. Risk of bias was evaluated. Odds ratios were analyzed for comparison of techniques and pooled event rates for non-comparative analyses. Pooled event rates were compared for each of included techniques.RESULTSOut of 1491 articles, 38 studies were included. A total of 47491 patients were included, of which 38683 (81.5%) underwent cystic duct closure with non-locking (metal) clips. All studies were of low-moderate methodological quality. Only two studies reported separate data on uncomplicated and complicated gallbladder disease. For overall CDL, an odds ratio of 0.4 (95%CI: 0.06-2.48) was found for harmonic energy vs clip closure and an odds ratio of 0.17 (95%CI: 0.03-0.93) for locking vs non-locking clips. Pooled CDL rate was around 1% for harmonic energy and metal clips, and 0% for locking clips and ligatures.CONCLUSIONBased on available evidence it is not possible to either recommend or discourage any of the techniques for cystic duct closure during LC with respects to CDL, although data point out a slight preference for locking clips and ligatures vs other techniques. No separate recommendation can be made for complicated gallbladder disease.