The purpose of present study was to evaluate the effects of maximal acute physical exercise on prothrombin time/international normalized ratio (PT/INR) in patients with primary antiphospholipid syndrome (PAPS) under oral anticoagulation with warfarin and the safety of acute exercise in regard to thrombosis and bleeding risk. Eighteen physically inactive women with PAPS (Sydney criteria) with exclusive venous events and without thrombocytopenia were included. All patients were under stable warfarin therapy (PT/INR target: 2.0-3.0). Eighteen age-matched healthy sedentary women without thrombosis/bleeding disorders were selected as controls. All subjects performed a maximal exercise test, and capillary blood samples were obtained pre-, post- and at 1-h post-exercise (recovery time) for PT/INR analysis using a portable CoaguCheck. PAPS patients and controls had similar mean age (31.50 ± 8.06 vs. 29.61 ± 7.05 years, p = 0.46) and body mass index (24.16 ± 3.67 vs. 24.66 ± 2.71 kg/m(2), p = 0.65). PAPS had a mild but significant increase in PT/INR value at 1-h post-exercise (recovery) compared with pre- (2.33 ± 0.34 vs. 2.26 ± 0.29, p = 0.001) and post-exercise (2.33 ± 0.34 vs. 2.26 ± 0.32, p = 0.001) that was observed in 61.11 % of these patients. None of the subjects had thrombotic or bleeding complications related to the acute exercise. Acute exercise in patients with PAPS with exclusive venous thrombosis was safe with a minor increase in PT/INR. This is an important step to introduce regular exercise training as a therapeutic tool in the management of these patients.