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Objective: To develop a dosage correlated with shoulder height (SH) in centimeters for effective immobilization of free-ranging giraffes, using a combination of medetomidine (MED) and ketamine (KET) and reversal with atipamezole (ATP)., Design: Prospective study., Animals: 23 free-ranging giraffes., Procedure: The drug combination (MED and KET) was administered by use of a projectile dart. Quality of induction, quality of immobilization, and time to recovery following injection of ATP were evaluated. Physiologic variables measured during immobilization included PaO2, PaCO2, oxygen saturation, end-tidal CO2, blood pH, indirect arterial blood pressure, heart and respiratory rates, and rectal temperature., Results: Sixteen giraffes became recumbent with a dosage (mean +/- SD) of 143 +/- 29 microg of MED and 2.7 +/- 0.6 mg of KET/cm of SH. Initially, giraffes were atactic and progressed to lateral recumbency. Three giraffes required casting with ropes for data collection, with dosages of 166 +/- 5 microg of MED and 3.2 +/- 0.6 mg of KET/cm of SH. Four giraffes required administration of etorphine (n = 2) or were cast with ropes (2) for capture but remained dangerous to personnel once recumbent, precluding data collection. In giraffes successfully immobilized, physiologic monitoring revealed hypoxia and increased respiratory rates. Values for PaCO2, end-tidal CO2, and heart rate remained within reference ranges. All giraffes were hypertensive and had a slight increase in rectal temperature. Atipamezole was administered at 340 +/- 20 microg/cm of SH, resulting in rapid and smooth recoveries., Conclusions and Clinical Relevance: Medetomidine and KET was an effective immobilizing combination for free-ranging giraffes; however, at the dosages used, it does not induce adequate analgesia for major manipulative procedures. Quality of induction and immobilization were enhanced if the giraffe was calm. Reversal was rapid and complete following injection of ATP.