Objective. Smoking, a major risk factor for cardiovascular morbidity and mortality, may be particularly harmful to women. Sympathetic and hemodynamic responses to cigarette smoking may be implicated in the link between smoking and acute cardiovascular events. We tested the hypothesis that acute effects of smoking on cardiovascular function are potentiated in women compared with men. Methods. We examined the effects of cigarette smoking and sham smoking on muscle sympathetic nerve activity, blood pressure and heart rate in 20 female and 20 male middle-aged healthy habitual smokers. Results. Sham smoking had no effect on muscle sympathetic nerve activity, blood pressure, or heart rate. Although cigarette smoking increased average systolic blood pressure and heart rate in both females and males, systolic blood pressure increased more in women (12+/-2 mmHg) than in men (6+/-2 mmHg; p = 0.02), as did heart rate (16+/-2 beats/min in women vs 9+/-2 beats/min in men; p = 0.002). Female smokers also had greater smoking-related increases in systolic blood pressure variability compared with males (2.2+/-0.6 vs 0.4+/-0.4 mmHg, respectively; p = 0.01) and greater decreases in RR variability (-28+/-5 vs -7+/-4 ms; p = 0.002). Despite the potentiated blood pressure increase in females, which would be expected to inhibit sympathetic activity to a greater extent in females than in males, changes in muscle sympathetic nerve activity during smoking were similar in both sexes. Conclusions. Acute pressor and tachycardic effects of smoking are potentiated in women compared with men. These findings may have important implications for understanding increased vulnerability to acute cardiovascular events in women who smoke.