Patent foramen ovale (PFO) is more frequent in cryptogenic stroke patients than in the general population. The aim of this study was to determine prothrombotic markers regarding PFO in young cryptogenic stroke patients. We prospectively included consecutive cryptogenic stroke patients younger than 55 years. PFO was diagnosed with simultaneous transcranial Doppler and transesophageal echocardiography. We analyzed the following prothrombotic markers: antiphospholipid antibodies (APS), protein C and protein S deficiencies, factor V Leiden FVG1691A, prothrombin gene mutation PTG20210A and coagulation factor XII mutation FXIIC46T. From June 2005 to July 2006 we studied 39 patients, mean age 44.7 ± 8.6 years, 48.7% men. PFO was detected in 17 patients (43.6%). We found no differences between PFO and non-PFO patients regarding prothrombotic markers: APS (P = 0.851), protein S deficiency (P = 0.851), protein C deficiency (P = 0.249), FVG1691A (P = 0.202), PTG20210A (P = 0.401) or FXIIC46T (P = 0.966). Female gender was the only variable related to prothrombotic markers, independent of PFO (P = 0.001). The only prothrombotic marker related to PFO size (large PFO) was APS (P = 0.043). Large PFO were also related to deep venous thrombosis (P = 0.040) and atrial septal aneurysm (P = 0.010). PFO patients do not present more prothrombotic markers than non-PFO patients, but APS are more frequent in large PFO.