Background To compare the effects of three anesthesia drug combinations in miniature pigs. Methods Guizhou miniature pigs (15 male, 15 female, 22-24 months)were randomly divided into three groups (n=10, 5 male, 5 female) and anesthetized intramuscularly (neck) with sumianxin Ⅱ (0.1 ml/kg) and 3% pentobarbital (0.8 ml/kg; Group A); ketamine (10 mg/kg) and 3% pentobarbital (0.8 ml/kg; Group B); or ketamine (10 mg/kg) combined with sumianxin II (0.1 ml/kg; Group C). Induction time, maintenance time, recovery time, and mortality were recorded. Heart rate, respiration, mean arterial pressure, and body temperature were analyzed pre-anesthesia (T0), after induction (T1), 30 min after operation (T2), 60 min after operation (T3), and at the end of anesthesia (resuscitation, T4). Results There were no significant differences in body weight, length, or experimental period between animals in the three treatment groups. The induction times of groups B and C (2-3 min) were significantly shorter than that of group A (7.4±1.1 min). The maintenance time of group B (136±11.4 min) was significantly different from those of groups A and C. The recovery time of group C was 4±1.0 min, compared with 9±0.6 min in group A and 10±1.5 min in group B. In group A, five pigs had adverse reactions (nausea and vomiting), and one pig died. All animals in group B had adverse reactions, and one pig died. The pigs in group C did not experience adverse reactions. The heart rates and respiration of the animals in group C were decreased at T2 and T3 compared with those of group A and B; there were no differences in heart rate and respiration between groups A and B. There were no differences in body temperature or mean arterial pressure of the pigs in the three treatment groups.Conclusions Intramuscular injection of ketamine combined with sumianxin Ⅱ is a suitable anesthesia therapy in miniature pigs because of short induction and recovery times, long maintenance time, and effectiveness.