BACKGROUND: Anterior cruciate ligament (ACL) reconstruction is commonly associated with moderate-to-severe postoperative pain. Notably, various pain control strategies, a femoral nerve block (FNB) with a lateral femoral cutaneous nerve block (LFCNB), adductor canal block (ACB) with LFCNB, or periarticular cocktail injection (PI), have been investigated. However, no studies compare the effects of FNB with LFCNB, ACB with LFCNB, and PI for pain control after ACL reconstruction. This study aimed to evaluate the impact of FNB with LFCNB, ACB with LFCNB, and PI for pain relief in the early postoperative period after ACL reconstruction. METHODS: This retrospective controlled clinical trial enrolled 299 patients who underwent primary ACL reconstruction at our hospital between April 2016 and October 2022. We categorized these cases into groups based on the use of PI (PI group), FNB with LFCNB (FNB group), and ACB with LFCNB (ACB group) for pain management. We selected 40 cases each, with matched age, sex, and body mass index (BMI) from each group, resulting in 120 cases for analysis. In the FNB and ACB groups, 0.75% ropivacaine 15 ml was injected under ultrasound guidance preoperatively. In the PI group, a mixture of 0.75% ropivacaine 20 ml, normal saline 20 ml, and dexamethasone 6.6 mg was injected half at the start of surgery and the rest just before wound closure. Patient demographics (age, sex, height, body weight, and BMI) and surgical data (the requirement for meniscal repair, operative time, and tourniquet inflation time) were analyzed. After ACL reconstruction, patients' numerical rating scale pain scores (NRS) (0-10) were recorded at 30 min and 4, 8, 12, 24, 48, and 72 h postoperatively. NRS were then compared among the three groups using analysis of variance. In addition, within each group, these data were compared between the NRS ≥7 and NRS ≤6 groups using a -test. RESULTS: There were no significant differences in patient demographics and surgical data. Pain scores were significantly higher in the PI group than in the FCB and ACB groups 30 min postoperatively, but they were lower at 12, 24, 48, and 72 h postoperatively. In the FNB group, there were no significant differences in the demographic and surgical data by NRS pain score. In the ACB group, the number of men was significantly higher in the NRS ≥7 group than in the NRS ≤6 group (p = 0.015). In the PI group, tourniquet inflation time was significantly longer in the NRS ≥7 group than in the NRS ≤6 group (p = 0.008). CONCLUSIONS: Following ACL reconstruction using a hamstring autograft, periarticular cocktail significantly reduced early postoperative pain compared with nerve block combinations.