Background: Laparoscopic cholecystectomy (LC) post Endoscopic retrograde cholangio-pancreatography (ERCP) with endoscopic sphincterotomy (ES) is accepted as treatment of choice for choledocho-cholecystolithiasis. Studies have demonstrated that LC after ES is associated with difficulties, complications and higher conversion rate. Our study was to assess the challenges and complexities of LC after ERCP compared with standard elective LC for symptomatic uncomplicated cholecystolithiasis and assess the stenting effect when inserted on the following cholecystectomy and detect other factors that may cause post ERCP cholecystectomy challenges and complexities. Patients and methods: Prospective controlled clinical trial was conducted over 50 patients : (Group A 25 patients) who had undergone a previous ERCP for choledocholithiasis (PES) and (Group B 25 patients) with cholecystolithiasis with no previous intervention before LC (NPES). Results: Patients in PES group had higher risks for longer operative time (mean 36 min) which is statistically highly significant, the conversion rate in the PES group and the NPES group (12% versus 0%), were not statistically significant, duration of post-operative hospital stay in the PES group was longer than NPES group (statistically highly significant), there was more difficulty in achieving the critical view of safety in the PES group (easily achieved in 52%) than NPES group (easily achieved in 92%) (Statistically different), the amount of post-operative drain was higher in the PES group (30-300 ml sero-sanginous fluid) than the NPES group (15-30 ml serosanginous fluid) (statistically highly significant). Conclusion: Laparoscopic cholecystectomy post ERCP especially when delayed or stent was inserted is a challenge for any surgeon with higher complexity and longer operative time and more conversions to open cholecystectomies with more difficulty to achieve critical view of safety. So, it has to be done by an experienced surgeon and rendezvous ERCP with laparoscopic cholecystectomy in same setting is advised with further prospective studies is needed with proper timing of interventions.