Background: Preoperative risk factors for the conversion of laparoscopic cholecystectomy to open surgery have been identified, but never been explored systematically. Our objective was to systematically present the evidence of preoperative risk factors for conversion of laparoscopic cholecystectomy to open surgery. Methods: PubMed and Embase were searched systematically in March 2014. Observational studies evaluating preoperative risk factors for conversion of laparoscopic cholecystectomy to open surgery in patients with gallstone disease were included. The outcome variables extracted were patient demographics, medical history, severity of gallstone disease, and preoperative laboratory values. Results: A total of 1,393 studies were screened for eligibility. We found 32 studies, including 460,995 patients operated with laparoscopic cholecystectomy, eligible for the systematic review. Of these, 10 studies were suitable for 7 meta-analyses on age, gender, body mass index, previous abdominal surgery, severity of disease, white blood cell count, and gallbladder wall thickness. Conclusions: A gallbladder wall thicker than 4-5 mm, a contracted gallbladder, age above 60 or 65, male gender, and acute cholecystitis were risk factors for the conversion of laparoscopic cholecystectomy to open surgery. Furthermore, there was no association between diabetes mellitus or white blood cell count and conversion to open surgery.