The clinical records of 103 Italian patients with inherited thrombophilia and thrombosis were reviewed to estimate the incidence of thrombotic recurrences and major bleeding complications according to the different duration of oral anticoagulant prophylaxis (OAP). The incidence of the first thrombotic recurrence was 2.9, 7.4 and 10.8 x 100 patients/year, respectively, in subjects receiving lifelong OAP, stopping OAP after a mean of 9 months (range 1-30 months) or not receiving OAP. The probability to remain free from thrombotic recurrences in patients undergoing lifelong OAP, as estimated by the Kaplan-Meier method, was significantly higher in comparison with untreated patients (p less than 0.001), but did not reach the statistical significance in comparison with patients who stopped prophylaxis. The incidence of further thrombotic recurrences was 1.2, 21.1 and 22.3 x 100 patients/year, respectively, in the three groups defined above. The difference between patients who prolonged indefinitely OAP vs those who stopped or did not receive OAP was statistically significant (p = 0.003). Two intracranial bleedings, one of which fatal, were observed in patients undergoing lifelong OAP, whereas no major bleeding complications occurred in the other two groups. Our study supports the recommendations to continue indefinitely OAP in patients with inherited thrombophilia and recurrent thrombosis, but suggests caution in starting lifelong prophylaxis soon after the first thrombotic event in all patients.