Purpose: The purpose of this study was to compare the postoperative analgesic effects of intraarticularly administered ketamine, neostigmine, and bupivacaine after outpatient arthroscopic surgery. Type of Study: Prospective, randomized, double-blind, clinical study. Methods: In this study, 60 patients undergoing arthroscopic surgery other than ligament reconstruction were evaluated for postoperative pain. Ketamine, neostigmine, and bupivacaine were administered intra-articularly. The period of effective analgesia, recorded in minutes, was measured between time 0 and first usage of patient-controlled anesthesia (PCA) by the patients. The visual analog scale (VAS) was used to describe the pain level of the patient. Results: VAS values were lower for the 3 medication groups compared with the placebo at rest and 90degrees knee flexion. Intra-articular administration of 0.5 mg/kg ketamine provided longer duration of analgesia as defined by the first PCA use time (P < .05). The total amount of pethidine and analgesia time were longer for the 3 medication groups. Conclusions: Our basic finding was reduction in postoperative pain and consumption of adequate analgesic drugs with intra-articular ketamine, bupivacaine, or neostigmine use. We have not seen any psychomimetic side effects, particularly as seen with higher doses or systemic use. This study may conclude that intra-articular administration of ketamine provides long-lasting and effective analgesia, similar to neostigmine but less effective than bupivacaine after knee arthroscopy without any adverse effects. Level of Evidence: Level I.