Background and Objectives: The diagnostic value of thrombophilia remains unknown in young patients with patent foramen ovale (PFO) and stroke. In this study we hypothesized that inherited thrombophilias that lead to venous thrombosis are more prevalent in patients with PFO. Materials and Methods: The study included patients of the tertiary center Vilnius University Hospital Santaros Klinikos who had a cryptogenic ischemic stroke between the ages of 18 and 50 between the years 2008 and 2021. Transient ischemic attacks were excluded. Contrast-enhanced transcranial Doppler ultrasound and extensive laboratory testing were performed. Results: The study included 161 cryptogenic stroke patients (mean age 39.2 ± 7.6 years; 54% female), and a right-to-left shunt was found in 112 (69.6%). The mean time between stroke and thrombophilia testing was 210 days (median 98 days). In total, 61 (39.8%) patients were diagnosed with thrombophilia. The most common finding was hyperhomocysteinemia (26.7%), 14.3% of which were genetically confirmed. Two patients (1.2%) were diagnosed with factor V Leiden mutation, three patients (1.9%) with prothrombin G20210A mutation, one patient (0.6%) had a protein C mutation and one patient (0.6%) had a protein S mutation. No antithrombin mutations were diagnosed in our study population. A total of 45.5% of patients with inherited thrombophilia had a right-to-left shunt, while 54.5% did not, p = 0.092. Personal thrombosis anamnesis was positive significantly more often in patients with antiphospholipid syndrome. Conclusions: The hypothesis of the study was rejected since inherited venous thrombophilia was not significantly more common in patients with PFO. Due to the rarity of thrombophilias in general, more research with a larger sample size is required to further verify our findings.