We evaluated thiafentanil oxalate (A-3080) for the immobilization of mule deer (Odocoileus hemionus) under laboratory and field conditions. In a crossover experiment comparing recommended (0.1 mg/kg) and 2× recommended thiafentanil doses in captive deer, both produced rapid induction and immobilization. Mean induction was shorter (P =0.013) for the 2× group (1.9 vs. 3 min); mean reversals for both groups were rapid (recommended=0.9 min after naltrexone injection; 2× =1 min) and did not differ (P=0.29). Six free-ranging mule deer were immobilized with 7 mg thiafentanil and four with 10 mg; mean induction was 2.3 min for both groups (95% confidence interval [CI]: 7 mg, 1.2–3.4; 10 mg, 1.9–2.8), and mean reversal was <1 min for both groups. Of 165 free-ranging deer darted with various combinations of thiafentanil and xylazine, we successfully immobilized 148 (90%). Mean induction ranged from 2.1 to 4.9 min for different drug combinations. Reversals were not compared because naltrexone and yohimbine doses varied, but overall mean reversal was 1.9 min (95% CI, 1.7–2.1 min) after injection of naltrexone and yohimbine intravenously (IV); naltrexone:thiafentanil ratios ranging from 10:1 to 43:1 provided mean recoveries ranging from 1.5 to 2.3 min. All 25 deer fitted with radio collars were alive at 30 days postcapture. On the basis of overall reliability and effectiveness, drug volumes, and ease of handling drugged animals, we recommend using a combination of 10–12 mg thiafentanil (0.15–0.2 mg/kg) and 100 mg xylazine to immobilize mule deer; immobilization can be effectively reversed with 100 mg naltrexone or more and 15 mg yohimbine or more IV. Where feasible, we also recommend the use of transmitter darts when immobilizing mule deer with opioids in order to maximize recovery of darted deer and to ensure that missed darts are found.