Background In patients undergoing laparoscopic cholecystectomy (LC) for complicated biliary disease, complication rates increase up to 30%. The aim of this study is to assess the effect of differences in surgical strategy comparing outcome data of two large volume hospitals. Methods A prospective database was created for all the patients who underwent a LC in two large volume hospitals between January 2017 and December 2018. In cases of difficult cholecystectomy in clinic A, regular LC or conversion were surgical strategies. In clinic B, laparoscopic subtotal cholecystectomy was performed as an alternative in difficult cases. The difficulty of the cholecystectomy (score 1-4) and surgical strategy (regular LC, subtotal cholecystectomy, conversion) were scored. Postoperative complications, reinterventions, and ICU admission were assessed. For predicting adverse postoperative complication outcomes, uni-and multivariable analyses were used. Results A total of 2104 patients underwent a LC in the study period of which 974 were from clinic A and 1130 were from clinic B. In total, 368 procedures (17%) were scored as a difficult cholecystectomy. In clinic A, more conversions were performed (4.4%) compared to clinic B (1.0%; p < 0.001). In clinic B, more subtotal laparoscopic cholecystectomies were performed (1.8%) compared to clinic A (0%; p = < 0.001). Overall complication rate was 8.2% for clinic A and 10.2% for clinic B (p = 0.121). Postoperative complication rates per group for regular LC, conversion, and subtotal cholecystectomy in difficult cholecystectomies were 45 (15%), 12 (24%), and 7 (35%; p = 0.035), respectively. The strongest predictor for Clavien-Dindo grade 3-5 complication was subtotal cholecystectomy. Conclusion Surgical strategy in case of a difficult cholecystectomy seems to have an important impact on postoperative complication outcome. The effect of a subtotal cholecystectomy on complications is of great concern.