Background: Laparoscopic cholecystectomy (LC) is the surgery of choice for patients suffering from gallstone diseases. Open cholecystectomy these days is performed after conversion from laparoscopic surgery due to various reasons. The aim of this study was to assess the factors responsible for conversion of LC to open surgery by identifying preoperative risk factors that could predict conversion and intraoperative technical/surgical difficulties and complications that cause conversion. Methods: A total of 310 patients were included in this prospective observational study conducted between November 2018 and March 2020. Results: Out of 310 cases, 38 were converted to open surgery with a conversion rate of 12.2%. Mean age was 10 years more in the converted group. Males had a higher chance of conversion than females (18.6 vs 7%). Conversion rate was significantly higher in patients with body mass index (BMI) >23 kg/m² (25%), with features of acute cholecystitis, who underwent interval cholecystectomy (25.8%), who underwent endoscopic retrograde cholangiopancreatography (ERCP) (>40%), with total white blood cell (WBC) counts ≥10,000/mm³ (25.6%), with serum albumin <3.5 g/dL (43.8%), with imaging findings of acute cholecystitis (25.6%), and with dilated common bile duct (CBD)/choledocholithiasis (33.3%). Conversion rate when LC was performed early after ERCP was 18% and when performed after 4–6 weeks was >50%. The most common causes for conversion were a frozen Calot's triangle due to dense inflammatory adhesions, leading to inadequate visualization of critical structures. Conclusion: Identifying patients with significant risk factors for conversion could minimize adverse effects of prolonged surgery by limiting duration of trial of laparoscopic dissection. Surgical residents need to identify low-risk patients preoperatively and require proper training before handling difficult cases. Clinical significance: Early LC should be considered in all patients who are able to withstand surgery, as delayed surgery increases the chances of conversion. Registration of the study: This prospective study has been registered in the Clinical Trials Registry of India (CTRI). CTRI Registration Number CTRI/2018/11/016338.