To define a protocol of anesthesia for long-duration invasive surgery in a lizard, eight young adult Argentine tegus (Salvator merianae) of mean body weight 3.0 kg (interquartile range [IQR] 3.40–2.65) were anesthetized with a mixture of ketamine (K) and medetomidine (M) at 19°C, injected intramuscularly and equally distributed in the four limbs. As the experimental surgery procedure required a prolonged deep anesthesia with a good myorelaxation (between 16 and 21 hr), reinjections were required and reflexes were checked during surgery. Times for anesthetic induction, anesthetic reinjection, and recovery periods were recorded for five different combinations of ketamine-medetomidine: 1) 66 mg/kg K 100 μg/kg M; 2) 80 mg/kg K 100 μg/kg M; 3) 100 mg/kg K 130 μg/kg M; 4) 125 mg/kg K 200 μg/kg M; and 5) 150 mg/kg K 200 μg/kg M. The effect on the recovery speed of the postoperative atipamezole injection was also evaluated. The median induction time was 30 (IQR 35–27.5) min with no statistical difference between all the concentrations tested. The first reinjection of half a dose was administered after a mean of 5 hr (5.64 hr, IQR 5.95–4.84) as were the subsequent reinjections of a quarter dose (3.99 hr, IQR 5.98–3.23). Intramuscular administration of the ketamine-medetomidine combination is a simple, rapid, and efficient anesthesia for long-term surgery (>12 hr). A mix of 100 mg/kg ketamine and 200 μg/kg medetomidine, with reinjections every 4 hr of half a dose of the previous injection can maintain a good quality of anesthesia for at least 16 hr. The injection of atipamezole after the surgery reverses the effects of medetomidine and permits a reduction of the recovery period.