Persistent activation of the renin-angiotensin system leads to downregulation of the angiotensin type-1 receptor, and consequently, to a decreased response to exogenous angiotensin II. In the present study, we investigated the association of angiotensin II responsiveness to clinical outcome after coronary artery bypass grafting (CABG). We studied the responsiveness to exogenous angiotensin II in human thoracic artery preparations of 114 CABG patients. Mean duration of follow-up was 7.3+/-0.1 years, during which 21 patients experienced a cardiovascular event. A diminished response to angiotensin II remained in multivariate Cox regression analysis, after adjustment for sex, age, blood pressure, and number of diseased coronary arteries, the strongest predictor for cardiovascular events (relative risk, 3.37 [95% confidence interval, 1.20 to 9.51]; P=0.022). Furthermore, diminished response to angiotensin II was associated with an increased mean arterial pressure (102.85+/-1.38 versus 97.40+/-1.37; P=0.003) and a nonsignificant increase in angiotensin-converting enzyme activity, suggestive for a persistently activated renin-angiotensin system. In conclusion, these results suggest that in patients undergoing CABG, a diminished vascular responsiveness of the thoracic artery to exogenous angiotensin II is related to an increased risk of future cardiovascular events.