OBJECTIVE: To evaluate the effects of induction of anesthesia with alfaxalone in alpacas. STUDY DESIGN: Prospective, randomized, crossover design. ANIMALS: Five healthy alpacas (96.7 ± 19.9 kg, 9.6 ± 3.1 years old). METHODS: The alpacas were anesthetized on three occasions with alfaxalone, propofol, or ketamine-diazepam by intravenous injection. Quality of induction and intubation was assessed using a simple descriptive scale, and quality of recovery was scored: 1 (very poor)-5 (excellent). The auricular artery was catheterized for measurement of systolic (SAP), mean (MAP), and diastolic (DAP) arterial pressures and collection of blood. Variables measured were hemoglobin oxygen saturation (SpO2 ), respiratory rate, and end-tidal carbon dioxide partial pressure (Pe'CO2 ), and ECG. Repeated measures anova was used to assess effects of drug and time. Significance was set at p < 0.05. RESULTS: Mean dose of alfaxalone sufficient to allow intubation was 2.1 mg kg(-1) . Induction was excellent with all protocols. Heart rate (HR), SAP and MAP were significantly higher following alfaxalone compared to ketamine-diazepam. Blood lactate concentration when standing following alfaxalone was higher compared to minutes 1 and 6, and to propofol (p < 0.05). All alpacas required oxygen supplementation and mechanical ventilation to treat SpO2 < 90% or Pe'CO2 > 60 mmHg. Time from induction to standing was longer with alfaxalone (34.1 ± 3.2 minutes) than propofol (19.0 ±4.3 minutes) or ketamine-diazepam (24.9 ±1.7 minutes). Recovery quality median scores were clinically and statistically different: 2 (alfaxalone), 4 (ketamine-diazepam), and 5 (propofol). Tremors, paddling, rolling, seizure-like activity and thrashing characterized recovery from alfaxalone. CONCLUSION: Recovery quality was worst with alfaxalone. HR, SAP, MAP were increased at minute 1 in all protocols. Transient hypercapnia and hypoxia was observed with all protocols. CLINICAL RELEVANCE: All protocols were adequate for induction of anesthesia. Alfaxalone alone in unpremedicated alpacas is not recommended.