Although thiafentanil oxalate has been widely used for wildlife immobilisation on different species, no report has been published about its usefulness on African buffalo (Syncerus caffer). Thirty-four African buffaloes were successfully immobilised at Loskop Dam Nature Reserve, South Africa in July 2013. The animals were kept in bomas of the nature reserve. The purpose of the immobilisation was to provide opportunity for microchip implantation, ear tag placement, intradermal tuberculin test and blood sampling. All animals were immobilised with thiafentanil oxalate 6 mg/animal (0.007-0.01 mg/kg) and azaperone 40 mg/animal (0.07-0.04 mg/kg) using Dan-inject darts and gun. The opioid reversal agent naltrexone hydrochloride 60 mg/animal (0.07-0.1 mg/kg) was given intravenously to the ear vein. The mean induction time was 3.9 ± 0.2 min, the recovery time was 1.65 ± 0.87 min. The results of the present study indicate that thiafentanil oxalate, this low-volume, high-potency, reversible drug combined with azaperone provides fast induction and smooth recovery. The authors recommend this drug combination as a reliable immobilising regimen for African buffalo.