Diagnosis of heparin induced thrombocytopenia (HIT) is not always easy, especially when a confirmatory functional test is not available. In most cases the diagnosis relies on the combination of pretest probability and an immunologic test. Among patients post cardiopulmonary bypass (CPB) surgery, anti-platelet factor 4/heparin antibodies tend to be high but with low clinical implication. The current retrospective study examined the behavior of patients with positive PF4/heparin-PaGIA results, divided into two groups according to whether or not they have undergone CPB surgery. The main focus of the study was on the reliability of the PF4/heparin-PaGIA test in these two settings. The files of 104 single center patients, who had a positive PF4/heparin-PaGIA test, were reviewed. 62 % were post CPB and 38 % were not. An association between the intensity of positivity of PF4/heparin-PaGIA test and both the 4Ts pretest probability method (p = 0.003) and the incidence of thrombosis (p = 0.02) was found only in the patients who have not undergone CPB surgery, but not in the CPB patients. This study suggests that PF4/heparin-PaGIA is not a reliable method in patients post CPB surgery who are investigated for a possible diagnosis of HIT.