For cardiopulmonary bypass, the polyvinyl chloride (PVC) circuit which can initiate the activation of platelets and the coagulation cascade after blood cell contacting is the possible detrimental effect. Surface coating of the PVC tubing system can be an effective approach to enhance circuit’s hemocompatibility. In this study, aluminum oxide (Al₂O₃) thin films were deposited through thermal atomic layer deposition (T-ALD) or plasma-enhanced ALD (PE-ALD) on PVC samples, and the anticoagulation of the Al₂O₃-coated PVC samples was demonstrated. The results revealed that Al₂O₃ deposition through ALD increased surface roughness, whereas T-ALD had a relative hydrophilicity compared with blank PVC and PE-ALD. Whole blood immersion tests showed that blood clots formed on blank PVC and that a large amount of red blood cells was found on PE-ALD substrates, whereas less blood cells were noted in T-ALD samples. Both T-ALD and PE-ALD Al₂O₃ films did not cause activation of blood cells, as evidenced in CD3⁺/CD4⁺/CD8⁺, CD61⁺/CD62P⁺, and CD45⁺/CD42b⁺ populations. Analysis of serum coagulation factors showed that a lower amount of prothrombin was absorbed on T-ALD Al₂O₃ samples than that on blank PVC. For albumin and fibrinogen immersion tests, immunostaining and scanning electron microscopy further revealed that a thin albumin layer was absorbed on T-ALD Al₂O₃ substrates but not on PVC samples. This study revealed that deposition of Al₂O₃ films by T-ALD can improve anticoagulation of the PVC tubing system.