OBJECTIVE To compare post-operative pain in cats after alfaxalone or ketamine- medetomidine anaesthesia for ovariohysterectomy (OHE) and physiologic parameters during and after surgery. METHODS Prospective 'blinded' randomized clinical study. METHODS Twenty-one healthy cats. METHODS Cats were assigned randomly into two groups: Group A, anaesthesia was induced and maintained with alfaxalone [5 mg kg(-1) intravenously (IV) followed by boli (2 mg kg(-1) IV); Group MK, induction with ketamine (5 mg kg(-1) IV) after medetomidine (30 μg kg(-1) intramuscularly (IM)], and maintenance with ketamine (2 mg kg(-1) IV). Meloxicam (0.2 mg kg(-1) IV) was administered after surgery. Basic physiological data were collected. At time T = -2, 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 20, and 24 hours post-operatively pain was assessed by three methods, a composite pain scale (CPS; 0-24 points), a visual analogue scale (VAS 0-100 mm), and a mechanical wound threshold (MWT) device. Butorphanol (0.2 mg kg(-1) IM) was administered if CPS was scored ≥13. Data were analyzed using a general linear model, Kruskal-Wallis analyses, Bonferroni-Dunn test, unpaired t-test and Fisher's exact test as relevant. Significance was set at p < 0.05. RESULTS VASs were significantly higher at 0.5, 1, 2, 4, and 20 hours in group A; MWT values were significantly higher at 8 and 12 hours in group MK. Post-operative MWT decreased significantly compared to baseline in both groups. There was no difference in CPS at any time point. Five cats required rescue analgesia (four in A; one in MK). CONCLUSIONS Anaesthesia with ketamine-medetomidine was found to provide better post-surgical analgesia than alfaxalone in cats undergoing OHE; however, primary hyperalgesia developed in both groups. Alfaxalone is suitable for induction and maintenance of anaesthesia in cats undergoing OHE, but administration of additional sedative and analgesic drugs is highly recommended.