Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background The ideal location for single-injection adductor canal block that maximizes analgesia while minimizing quadriceps weakness after painful knee surgery is unclear. This triple-blind trial compares ultrasound-guided adductor canal block injection locations with the femoral artery positioned medial (proximal adductor canal), inferior (mid-adductor canal), and lateral (distal adductor canal) to the sartorius muscle to determine the location that optimizes postoperative analgesia and motor function. The hypothesis was that distal adductor block has (1) a superior opioid-sparing effect and (2) preserved quadriceps strength, compared with proximal and mid-locations for anterior cruciate ligament reconstruction. Methods For the study, 108 patients were randomized to proximal, mid-, or distal adductor canal injection locations for adductor canal block. Cumulative 24-h oral morphine equivalent consumption and percentage quadriceps strength decrease (maximum voluntary isometric contraction) at 30 min postinjection were coprimary outcomes. The time to first analgesic request, pain scores, postoperative nausea/vomiting at least once within the first 24 h, and block-related complications at 2 weeks were also evaluated. Results All patients completed the study. Contrary to the hypothesis, proximal adductor canal block decreased 24-h morphine consumption to a mean ± SD of 34.3 ± 19.1 mg, (P < 0.0001) compared to 64.0 ± 33.6 and 65.7 ± 22.9 mg for the mid- and distal locations, respectively, with differences [95% CI] of 29.7 mg [17.2, 42.2] and 31.4 mg [21.5, 41.3], respectively, mostly in the postanesthesia care unit. Quadriceps strength was similar, with 16.7%:13.4%:15.3% decreases for proximal:mid:distal adductor canal blocks. The nausea/vomiting risk was also lower with proximal adductor canal block (10 of 34, 29.4%) compared to distal location (23 of 36, 63.9%; P = 0.005). The time to first analgesic request was longer, and postoperative pain was improved up to 6 h for proximal adductor canal block, compared to mid- and distal locations. Conclusions A proximal adductor canal injection location decreases opioid consumption and opioid-related side effects without compromising quadriceps strength compared to mid- and distal locations for adductor canal block in patients undergoing anterior cruciate ligament reconstruction.