We performed 345 immobilizations on 150 North American porcupines (Erethizon dorsatum) using a mixture of ketamine hydrochloride (KH) and xylazine hydrochloride (XH). A subsample of 184 immobilizations performed on 124 individuals from 4 May to 7 November 2000 and from 22 January to 30 April 2001 is thoroughly analyzed. In contrast to published procedures, we found that injecting drugs into tail muscles was more efficient than into longitudinal muscles of the lower back, because tail injections decreased the need of multiple injections by 26%. Using tail injections, we were able to reduce the dose by 50% from other published reports without significantly affecting induction, immobilization, standing, or recovery times. We suggest that injection of 5 mg KH/kg and 2 mg XH/kg in the tail as a standard procedure to immobilize North American porcupines. Body mass significantly affected the induction and standing times for single injections performed in the tail, irrespective of dose or sex. Sex, dose, and mass had no effect on the quality of immobilizations and the respiration rate of individuals during immobilization. We report a 0.87% mortality rate using a mixture of KH and XH and suggest ways to further decrease this rate.