Netgun capture is a commonly used capture method for mule deer (Odocoileus hemionus) in North America. Mortalities during netgun captures are generally low, and most often caused by direct trauma and occasionally fatal capture myopathy. Capture is a stressful event for a wild animal, and subclinical capture myopathy is difficult to measure. The use of tranquilizers during netgun capture is not widespread. We compared physiologic variables from 250 netgun-captured deer (57 males and 193 females) that did or did not receive midazolam and azaperone (mean, 0.14 mg/kg; SD, 0.02 mg/kg; range, 0.08–0.21 mg/kg) at time of capture and before transporting to a processing location, with the goal of evaluating whether drug administration would improve or worsen the physiologic state of the animal. Deer were captured in association with management activities between December 2018 and March 2020, with 132 deer receiving midazolam and azaperone at time of capture. Variables recorded included chase times, time from capture to arrival at the processing location, time from capture to release, serial rectal temperatures, heart rates, respiratory rates, body condition, age, sex, O2 administration, creatine kinase, aspartate aminotransferase, packed cell volume, red blood cell concentration, and hemoglobin, as well as serial venous pH, pCO2, HCO3–, and base excess. All animals were collared with GPS tracking devices and monitored after release. There was no difference in survival after capture between deer that did or did not receive midazolam and azaperone. All animals experienced severe metabolic lactic acidosis, which generally worsened with increasing chase time, highlighting the critical importance of limiting chase times during captures. Drug administration did not influence the degree of metabolic acidosis; however, it appeared to have a favorable effect on several stress-related indices, including rectal temperature, heart rate, respiratory rate, and packed cell volume.