We recently reported prospective results from a cohort of patients scheduled for elective cardiac surgery with cardiopulmonary bypass (CPB) in which most baseline clinical parameters of patients and surgery outcomes failed to demonstrate relationships with post-CPB antithrombin (AT) activity. In this extension study, a larger sample size (250 patients) was analyzed following general linear models. Patients' sociodemographic and pre-CPB clinical data as well as pre/post-CPB AT activity and outcomes were collected. There was a significant decrease of post-CPB AT activity (95.6 ± 13.7-64.6 ± 12.1%; P < 0.001). Univariate and multivariate analyses revealed that a decrease of approximately 1% post-CPB AT activity may be expected per 3 years increase in patient's age. Univariate analysis showed that post-CBP AT activity was inversely related to the need for transfusions, acute renal failure and occurrence of any complication (re-intervention, low cardiac output, arrhythmia, lung dysfunction, stroke, acute renal failure, mesenteric ischemia and re-hospitalization; P < 0.05). Multivariate analysis adjusted for age and pre-CPB AT did not show statistical significance. Odds ratio (OR) less than 1 was observed in most outcomes (0.8 on average), which suggested a reduction of the probability for an increase of 10% in post-CBP AT. Our results confirm the role of low postsurgery AT activity influencing outcomes in patients undergoing CPB.