From 1968 to 1993, 179 newly diagnosed patients with polycythemia vera (PV) were enrolled in a prospective study using pipobroman as first chemotherapy. Among them, 140 fulfilled the Polycythemia Vera Study Group criteria for PV, and 39 patients (22%) can be considered as idiopathic erythrocytosis (IE). Vascular events occurred in 10% of IE and 20% of PV patients and solid tumors in 7.7% of IE and 12.8% of PV patients. There were no differences between PV and IE patients with regard to progression to myelofibrosis (MF), leukemic events and overall survival. Overall, 98.3% of patients initially responded to pipobroman, with very mild toxicity. A total of 164 PV patients who received more than 1 year of pipobroman were analyzed for long-term evolution. The actuarial risk of thrombosis was 15.6 and 23.8% at 10 and 18 years, respectively. In all, 21 patients developed a solid tumor during follow-up, added and/or switched drugs being a risk factor. Actuarial risk of MF was as low as 4.9 and 9.4% at 10 and 15 years, respectively. Actuarial risk of leukemia was 14.4 and 18.7% at 10 and 15 years, respectively. Hyperleukocytosis at diagnosis was the only variable significantly associated with higher risk of leukemia. The median survival was 15.5 years, with two initial adverse prognostic factors: age above 60 years and hyperleukocytosis. Despite an increasing risk of leukemia with time, survival was not lower when compared to the French matched population. Only age and hyperleukocytosis at diagnosis were found to have a prognostic value in PV.