Grevy's zebra (Equus grevyi) is an endangered species often found in zoological collections. Veterinary care for this species often requires immobilization. This study retrospectively evaluated behavioral and physiological parameters from Grevy's zebra records after three immobilization protocols: etorphine and alpha-2 agonist (EA2; n = 11); etorphine, alpha-2 agonist, and ketamine (EA2K; n = 16); and thiafentanil, alpha-2 agonist, and ketamine (TA2K; n = 6). Median time to working depth was statistically different (P = 0.03; EA2 = 6.5 min, EA2K = 6.3 min, TA2K = 14.5 min) by the Kruskal–Wallis test. When EA2 + EA2K were combined and compared with TA2K (Wilcoxon rank sum test), median recumbency time (P = 0.02) was also significantly longer (15 min compared with 6 min) for TA2K. There were no significant differences between the groups for physiological parameters or recovery time after reversal. Although all protocols produced anesthesia in Grevy's zebra, increased time to achieve working depth was observed with the alpha-2 and thiafentanil combinations.