Background: Anterior cruciate ligament reconstruction (ACLR) is often performed on an outpatient basis; thus, effective pain management is essential to improving patient satisfaction and function. Local infiltration analgesia (LIA) and femoral nerve block (FNB) have been commonly used for pain management in ACLR. However, the comparative efficacy and safety between the 2 techniques remains a topic of controversy. Purpose: To compare pain reduction, opioid consumption, and side effects of LIA and FNB after ACLR. Study Design: Systematic review; Level of evidence, 3. Methods: A systematic search of MEDLINE, Embase, and Cochrane Library databases was performed to identify studies comparing pain on the visual analog scale (a 100-mm scale), total morphine-equivalent consumption, and side effects between the 2 techniques after ACLR at the early postoperative period. The LIA was categorized into intra-articular injection and periarticular injection, and subgroup analyses were performed comparing either intra-articular injection or periarticular injection with FNB. Two reviewers performed study selection, risk-of-bias assessment, and data extraction. Results: A total of 10 studies were included in this systematic review and meta-analysis. In terms of VAS pain scores, our pooled analysis indicated that FNB was significantly more effective at 2 hours postoperatively compared with LIA (mean difference, 8.19 [95% confidence interval (CI), 0.75 to 15.63]; P = .03), with no significant difference between the 2 techniques at 4, 8, and 12 hours postoperatively; however, LIA was significantly more effective at 24 hours postoperatively compared with FNB (mean difference, 5.61 [95% CI, −10.43 to −0.79]; P = .02). Moreover, periarticular injection showed a significant improved VAS pain score compared with FNB at 24 hours postoperatively (mean difference, 11.44 [95% CI, −20.08 to −2.80]; P = .009), and the improvement reached the threshold of minimal clinically important difference of 9.9. Total morphine-equivalent consumption showed no difference between the 2 techniques, and side effects were unable to be quantified for the meta-analysis because of a lack of data. Conclusion: Compared with FNB, LIA was not as effective at 2 hours, comparable within 12 hours, and significantly more effective at 24 hours postoperatively for reducing pain after ACLR. Total morphine-equivalent consumption showed no significant differences between the 2 techniques.