Background: Laparoscopic Cholecystectomy (LC) becomes the standard of care for patients requiring removal of gallbladder. LC may be rendered difficult by various problems encountered during procedure. Several factors have been implicated with a difficult case, but no reliable criteria are available yet to identify patients preoperatively with a difficult LC. Preoperative prediction of a difficult LC can help the patient as well as the surgeon prepare better for the intraoperative challenges and tailored approach accordingly. The present study was undertaken to determine the association between preoperative clinical, laboratory and abdominal sonographic findings in patients undergoing LC for cholelithiasis and the technical difficulty at operation and to predict the most important indicators that affect the operation outcome in order to make the procedure safer for the patient as well as the surgeon. Methods: In 300 consecutive patients who underwent LC during 2014 to 2016 patient"s characteristics, clinical history, laboratory data, ultrasonography results and intraoperative details were prospectively analyzed to evaluate predictors of difficult LC. Results: Gender, age, obesity, history of hospitalization for acute cholecystitis, history of previous ERCP, history of previous abdominal surgery, Gall bladder size, GB wall thickening, pericholecystic fluid collection, large multiple GB stones and liver US findings; The above mentioned factors were found to have a statistical significant association with the final operation out come. Conclusions: Obesity, presence of history of previous abdominal surgery, gall bladder wall thickness and gallbladder stone size by preoperative ultrasound; were found to be the predictive factors of difficult LC in our study.