We assessed frequency and predictive factors for major cardiovascular (CV) events in 707 patients with primary myelofibrosis (PMF) followed in 4 European institutions. A total of 236 deaths (33%) were recorded for an overall mortality of 7.7% patient-years (pt-yr). Fatal and nonfatal thromboses were registered in 51 (7.2%) patients, with a rate of 1.75% pt-yr. If deaths from non-CV causes were considered as competing events, we estimated that the adjusted rate of major thrombotic events would have been 2.2% pt-yr. In a multivariable model, age older than 60 years (hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.24-4.39, P = .01) and JAK2 mutational status (HR, 1.92; 95% CI, 1.10-3.34; P = .02) were significantly associated with thrombosis, whereas the strength of the association between leukocyte count higher than 15 x 10(9)/L and CV events was of borderline significance (HR, 1.72; 95% CI, 0.97-2.72; P = .06). The highest incidence of fatal and nonfatal thrombosis was observed when the mutation was present along with leukocytosis (3.9% pt-yr; HR, 3.13; 95% CI, 1.26-7.81). This study is the largest hitherto carried out in this setting and shows that the rate of major CV events in PMF is comparable with that reported in essential thrombocythemia, and it is increased in aged patients and those with JAK2 V617F mutation and leukocytosis.