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Objective—To compare postoperative discomfort assessed by subjective pain score and plasma cortisol concentrations in cats undergoing onychectomy that received analgesia by use of transdermal fentanyl (TDF) patches or an IM injection of butorphanol. Design—Randomized prospective clinical trial. Animals—22 client-owned cats weighing 2.2 to 5 kg (4.84 to 11 lb) undergoing onychectomy. Procedure—Researchers were blinded to which cats received a TDF patch (25 µg/h) 18 to 24 hours prior to surgery or an IM injection of butorphanol (0.2 mg/kg [0.09 mg/lb]) at the time of sedation, immediately following extubation, and at 4-hour intervals thereafter for 12 hours. Clinical variables, plasma cortisol concentration, and pain scores were evaluated and recorded 24 hours prior to surgery, at extubation, and 2, 4, 8, 12, 24, 36, and 48 hours after surgery. Results—The TDF group had a lower pain score than the butorphanol group only at 8 hours after surgery. Both groups had significantly lower mean plasma cortisol concentrations 0, 24, 36, and 48 hours after surgery, compared with mean plasma cortisol concentrations prior to surgery. No significant differences in appetite or response to handling the feet were observed between the 2 groups. Conclusions and Clinical Relevance—Our data did not reveal a difference in pain relief between administration of TDF and butorphanol. Plasma cortisol concentrations were not different between groups. Fentanyl appeared to provide equivalent analgesia to butorphanol in cats undergoing onychectomy. The primary advantage of using a TDF patch is that repeated injections are not required. (J Am Vet Med Assoc 2002;220:1020–1024)