OBJECTIVE: To compare the quality of postoperative analgesia and sedation after preoperative saphenous and sciatic nerve blockade, preoperative lumbosacral epidural injection and perioperative intravenous (IV) morphine, lidocaine and ketamine infusions in dogs undergoing stifle arthroscopy and tibial plateau leveling osteotomy (TPLO) under general anesthesia. STUDY DESIGN: Prospective, blinded, randomized, clinical comparison study. ANIMALS: A total of 45 dogs weighing 33.9 (15.9-56.7) kg and aged 5.2 (1.0-12.0) years, mean (range), undergoing elective unilateral TPLO for spontaneous cranial cruciate ligament rupture. METHODS: Client-owned dogs were enrolled. Dogs were randomly assigned to one of three groups: group MLK, perioperative IV morphine, lidocaine and ketamine infusion; group EPID, lumbosacral epidural with ropivacaine and morphine; or group SSNB, saphenous and sciatic nerve blockade with ropivacaine. Routine stifle arthroscopy followed by TPLO surgery was performed. Sedation and pain scores were assessed at 0, 2, 4, 8 and 24 hours following extubation. Rescue analgesia was administered as prescribed by Glasgow composite pain score-short form score >5. RESULTS: Sedation scores for MLK were higher than EPID and SSNB. Pain scores for SSNB were lower than those for EPID and MLK. No significant differences were found in anesthesia duration or surgery duration among groups. No dogs required rescue analgesia. CONCLUSIONS AND CLINICAL RELEVANCE: Although analgesia was adequate in all groups, the best combination of analgesia without increased sedation was recorded for SSNB.