Background: Cholelithiasis is present in10 to 15% of the general population and asymptomatic in the majority. But in India, the incidence is around 4%. Approximately 1-2% of patients will develop symptoms requiring cholecystectomy per year. The advantages of laparoscopic cholecystectomy over open cholecystectomy are an earlier return to bowel functions, less postoperative pain, improved cosmesis, less length of hospital stay, earlier return to full activity, and decreased overall cost, reduced infection. The rate of conversion from laparoscopic cholecystectomy to open cholecystectomy is 5 to 10%. Hence it is necessary to study the predictive factors for difficult laparoscopic cholecystectomy. Therefore, this study was undertaken. Study Design: The study design is of case series. Aim of the Study: To determine the role of clinical, hematological and radiological factors role in predicting difficult laparoscopic cholecystectomy and the possibility of conversion to open cholecystectomy before surgery. Results: This study was done in the Department of General Surgery, M.G.M. Hospital, Warangal, Telangana state from September 2017 to August 2019. A total number of 220 cases were included in this study, which satisfied the inclusion and exclusion criteria. The following conclusions were derived from the present study. Conclusion: The highest incidence of gallstone is in the age group of 21 to 30 years, which is closely followed by 51 to 60 years and 41-50 years. The sex ratio (Male: Female) is 1:2 clearly shows female preponderance, which is the same all over the world. Endogenous estrogen and progestin are attributed to this phenomenon. The pain was the predominant symptom seen in all (100%) patients. Vomiting was present in 30% of the patients with pain. Dyspepsia was present in 20.4% of the patients and fever in 11.3% of them. Tenderness in the right hypochondrium was present in 25.4% of the patients while guarding and mass was present in 0.9 and 1.3%, respectively. Ultrasound is the most accurate and sensitive investigation for the diagnosis of cholelithiasis. Of the 220 patients, 213 had stones in the gallbladder, 29 patients had wall thickening, and 17 had a peri-cholecystic collection. In the present study, Prior Hospitalization, BMI > 27.5, Palpable Gall Bladder, Thick GB Wall, raised TLC, and Peri-Cholecystic Collection were significant predictors of difficult laparoscopic cholecystectomy. The positive predictive value for easy prediction was 94.7%, and for difficult prediction was 100%.