Although research on lemurid primates in Madagascar has been ongoing for several decades, reports on different drug regimes to immobilize wild lemurs are limited. This study compares the efficacy, reliability, and side effects of ketamine–xylazine, ketamine–xylazine–atropine, and tiletamine–zolazepam immobilization in wild Verreaux's sifakas (Propithecus verreauxi). In the course of a long-term study in Kirindy Forest, western Madagascar, eight animals each received a mixture of ketamine (5.32 ± 1.71 mg/kg) and xylazine (0.56 ± 0.19 mg/kg) (KX; 7 males, 1 female) and ketamine (6.58 ± 1.36 mg/kg), xylazine (1.28 ± 0.28 mg/kg), and atropine (0.013 ± 0.003 mg/kg) (KXA; 5 males, 3 females), respectively, and 14 individuals received tiletamine–zolazepam (7.73 ± 1.37 mg/kg) (TZ; 9 males, 5 females). Induction was smooth in all protocols, but showed considerable variation in duration when animals had received KXA. Immobilization as well as recovery lasted significantly longer with TZ than with KX (P < 0.05). Occurrence of side effects was not significantly different between the protocols; however, excessive salivation, involuntary muscular contractions, and vocalization only occurred in animals immobilized with TZ. Heart rate measurement at 10 min after onset of complete immobilization yielded significantly higher values if the animals had been immobilized with TZ compared to KX (P < 0.05). Heart rate decreased from the first to the second measurement for the KX- and KXA-immobilized animals, whereas immobilization with TZ resulted in an increase in heart rate. The results suggest that KX produces good, but short, immobilization in Verreaux's sifakas at approximately 5 mg/kg ketamine and 0.5 mg/kg xylazine and a smoother and shorter recovery phase than 5 to 10 mg/kg TZ, whereas adding atropine to KX did not provide any benefits.