BACKGROUND AND PURPOSE: Medial compartment femoro-tibial osteoarthritis (OA) is a common disease and opening-wedge high tibial osteotomy (OWHTO) is the common surgical procedure carried out for these patients. While most researchers are focusing on the surgical techniques during operation, the aim of this study is to evaluate the pain control effect of femoral nerve block (FNB) for OWHTO patients. METHODS: In this prospective, single-center, randomized controlled trial (RCT) study, 41 patients were operated on by OWHTO for OA during 2017 to 2018. Twenty of them (group A) accepted epidural anesthesia with FNB and 21 patients (group B) only had their single epidural anesthesia. All blocks were successful and all the 41 patients recruited were included in the analysis and there was no loss to follow-up or withdrawal. Systematic records of visual analog scores (VAS), quadriceps strength, mean number of times of patient-controlled intravenous analgesia (PCIA), using of additional opioids or nonsteroidal anti-inflammatory drugs (NSAIDs), and complications were done after hospitalization. The Student t test and Chi-Squared test was used and all P values ≤.05 were considered statistically significant. RESULTS: VAS scores at rest (3.48 ± 1.0 vs 4.68 ± 1.1) and on movemment (4.51 ± 0.6 vs 4.97 ± 0.8) decreased more in group A than group B with significance at follow-up of 12 hours. The quadriceps strength, consumption of additional opioids or NSAID injections and mean number of times that the patients pushed the PCIA button didnot differ significantly within each group. CONCLUSION: This RCT study shows that FNB in patients undergoing OWHTO for unicompartmental osteoarthritis of the knee could result in significant reduction in VAS scores at 12 hours postoperatively.Research registry, Researchregistry4792. Registered April 7, 2019 - Retrospectively registered, http://www.researchregistry.com.