AIM: To evaluate the efficacy of esketamine as an adjuvant for adductor canal block (ACB) in alleviating postoperative pain in patients undergoing arthroscopic knee surgery. METHODS: This single-center prospective randomized controlled trial enrolled 100 patients who underwent arthroscopic knee surgery at The General Hospital of Northern Theater Command of the Chinese People's Liberation Army from October 2022 to March 2023. Patients were randomly and evenly divided into four groups. Patients in the R group received ACB of 0.375% ropivacaine 20 mL before awakening, while patients in the L, M, and H groups received 0.375% ropivacaine 20 mL mixed with 20 mg, 30 mg, and 40 mg of esketamine respectively. RESULTS: The sensory block duration of the M and H groups was significantly longer than that of the R group (p = 0.042 and p = 0.003, respectively). Immediately and 8 hours after surgery, the resting and motor pain scores of the M and H groups were significantly reduced (p < 0.05), while the L group also showed a significant decrease at 8 hours after surgery (p = 0.003 and p = 0.032, respectively). Immediately after surgery, subjects of the H group were more deeply sedated than those of both the R and L groups (p = 0.039 and p = 0.041, respectively). However, the recovery quality of group H one day after surgery was worse compared with the other three groups (p < 0.001, p = 0.001 and p = 0.030, respectively). CONCLUSIONS: Compared to the use of ropivacaine alone, esketamine adjuvant can prolong the duration of ACB and reduce early postoperative pain. However, high-dose esketamine affects the quality of postoperative recovery and increases the risk of adverse effects. Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200065236).