As surgery in sickle cell patients is associated with high morbidity, this study aims to establish the safety of minimally invasive surgery in this high-risk group. Over a four-year period, 71 sickle cell patients underwent laparoscopic cholecystectomy (LC) for cholelithiasis. Five patients had asymptomatic gallstones. Preoperative gastroscopy and endoscopic retrograde cholangiography were performed in 7 and 14 patients, respectively. Forty-two patients were given simple blood transfusions, while 13 received partial exchange transfusions. The mean operative time was 80 minutes and the conversion rate was 5.6%. There were 10 (14%) postoperative complications, the majority of which were respiratory and wound-related. One patient (1.4%) died as a result of postoperative vaso-occlusive crisis. The median hospital stay was 2.5 days. We believe that laparoscopic cholecystectomy is safe in patients with sickle cell hemoglobinopathy who are particularly at risk of developing pigmented gallstones. Therefore, the use of minimally invasive surgery is encouraged in any sickle cell patient undergoing operative intervention.