Abstract Background Laparoscopic cholecystectomy is first‐line treatment for uncomplicated gallstone disease in high‐income countries due to benefits such as shorter hospital stays, reduced morbidity, more rapid return to work, and lower mortality as well‐being considered cost‐effective. However, there persists a lack of uptake in low‐ and middle‐income countries. Thus, there is a need to evaluate laparoscopic cholecystectomy in comparison with an open approach in these settings. Methods A cost–effectiveness analysis was performed to evaluate laparoscopic and open cholecystectomies at Rwanda Military Hospital (RMH), a tertiary care referral hospital in Rwanda. Sensitivity and threshold analyses were performed to determine the robustness of the results. Results The laparoscopic and open cholecystectomy costs and effectiveness values were $2664.47 with 0.87 quality‐adjusted life years (QALYs) and $2058.72 with 0.75 QALYs, respectively. The incremental cost–effectiveness ratio for laparoscopic over open cholecystectomy was $4946.18. Results are sensitive to the initial laparoscopic equipment investment and number of cases performed annually but robust to other parameters. The laparoscopic intervention is more cost‐effective with investment costs less than $91,979, greater than 65 cases annually, or at willingness‐to‐pay (WTP) thresholds greater than $3975/QALY. Conclusions At RMH, while laparoscopic cholecystectomy may be a more effective approach, it is also more expensive given the low caseload and high investment costs. At commonly accepted WTP thresholds, it is not cost‐effective. However, as investment costs decrease and/or case volume increases, the laparoscopic approach may become favorable. Countries and hospitals should aspire to develop innovative, low‐cost options in high volume to combat these barriers and provide laparoscopic surgery.