We compared the sedative and respiratory effects of intramuscular midazolam in men and women in a randomized, single-blind trial. The patients (203 men and 195 women) received a single dose of midazolam (0.05, 0.075, 0.1, or 0.15 mg·kg⁻¹) intramuscularly 45 min before arriving at the operating room. Assessments in the operating room included sedation level and respiratory status rated on an objective four-point scale. Men given 0.075, 0.1, or 0.15 mg·kg⁻¹ of midazolam exhibited greater sedation than did women given comparable doses. Midazolam 0.15 mg·kg⁻¹ depressed respiration more frequently in men than in women. Plasma concentrations of midazolam were determined in 10 men, and 10 women randomly selected from the patients who received 0.15 mg·kg⁻¹ of midazolam. A higher plasma concentration of midazolam, associated with a higher degree of sedation and respiratory depression, was attained in men than in women. These findings suggest that the optimal dose per unit body weight of intramuscular midazolam as premedication should be lower in men than in women to prevent over-sedation and respiratory depression.