Seventeen adult chimpanzees (Pan troglodytes) with an average age of 37 yr were immobilized with a combination of tiletamine-zolazepam (TZ) and medetomidine (MED) by one of two modes of delivery. Group A animals received the drug combination intramuscularly at 3 mg/kg and 0.05 mg/kg, respectively. Animals in group B received MED by oral transmucosal administration, meaning oral delivery with presumptive transmucosal absorption. MED at 0.1 mg/kg was mixed with marshmallow crème, and delivery was followed by 3 mg/kg of TZ intramuscularly. Chimpanzees from both groups were recovered after administration of atipamezole at 0.3 mg/kg intramuscularly. All chimpanzees were compliant with oral transmucosal drug administration, although two chimpanzees preferred oral MED mixed with applesauce. All animals exhibited some anxiety and excitatory behavior associated with darting, but this was reduced in group B, which was premedicated with oral transmucosal MED. The mean time from TZ administration to sedation sufficient for human contact was 16.4 and 14.7 min with and without oral transmucosal premedication, respectively. The mean time for recovery for those chimpanzees given oral transmucosal premedication was 13.8 min, which was significantly shorter than the time of recovery for the group not given oral premedication (P  =  0.02). Oral transmucosal administration of MED provided light sedation in 16 of 17 chimpanzees to the level of arousable recumbency and a heavier sedation in one chimpanzee with no adverse side effects. TZ combined with MED by either oral transmucosal or injectable administration provided safe, heavy, long sedation with rapid, smooth, uneventful recoveries.