OBJECTIVE Initiation of cardiopulmonary bypass (CPB) for open-heart surgery requires that heparin be administered and reach an adequate value of activated clotting time (ACT). We previously introduced a new heparin formula that considered the preoperative ACT. In this study, we determined other factors affecting ACT. METHODS Adult patients who underwent cardiac surgery using CPB were divided into two groups according to their ACT value after the initial administration of heparin during surgery. ACT above 450 s was defined as "Reach", and this group was compared to the "Short" group with ACT below 450 s. RESULTS The Reach and Short groups included 334 (64.7%) and 182 (35.3%) cases, respectively. Univariate analysis indicated that preoperative heparin use, age ≥ 80 years, New York Heart Association classification 4, white blood cell counts above the higher limit, hematocrit below the lower limit, platelet cell counts below the lower limit, low albumin levels, moderate renal dysfunction, high C-reactive protein levels, high brain natriuretic peptide levels, and moderate deterioration of left ventricular ejection fraction were associated with the effects of heparin. Multivariate analysis revealed that age ≥ 80 years (odds ratio [OR] 2.53, 95% confidence interval [95%CI] 1.41-5.24), New York Heart Association classification 4 (OR = 4.44, 95%CI 1.59-15.35), and platelet count below the lower limit (OR 0.37, 95%CI 0.31-0.85) were associated with the effects of heparin. CONCLUSIONS Old age, heart failure, and lower platelet counts affected heparin activity. The dose of heparin should be considered in those patients to reach the target ACT.