This study delves into heparin resistance (HR) during cardiopulmonary bypass (CPB) surgeries, analyzing 371 patients to identify contributing factors. HR, defined as the inability to achieve an activated clotting time of >480 seconds with an initial unfractionated heparin dose, was observed in 9.7% of cases. Key findings include the significant association of preoperative use of unfractionated heparin, certain blood parameters (e.g., white blood cell counts, fibrinogen levels), and notably, albumin and fibrinogen as independent predictors for HR. The research highlights the need for precise preoperative assessments to mitigate HR risks in CPB.