Benefits and harms of long-term anticoagulant therapy (AT) after acute pulmonary embolism (PE) are poorly known. The aim of this study was to investigate the outcome of patients with PE treated with AT for 5 years according to American College of Chest Physicians (ACCP) guidelines.Patients with both unprovoked and secondary PE were consecutively enrolled in a "real life" study. After a 12-month AT, they continued or stopped the treatment according to ACCP guidelines, and were followed-up for 5 years. Outcomes were all-cause mortality, recurrence, and fatal recurrence under AT.Of the original consecutive 585 patients, 471 were included (83 dead, 31 lost during the 1st year). Of these, 361 (76.6%) continued AT. During 5 years, death occurred in 109 (30.2%) patients, with a mortality rate of 8.00 events/100 person-years of follow-up; recurrence in 34 (9.4%), with an incidence rate of 2.58 events/person-years; fatal recurrence in 13 (3.6%), with an incidence rate of 0.95 events/person-years. The case fatality rate for recurrence was 38.2%. In the subgroup of patients with unprovoked PE, the chance of dying was significantly lower (RR 0.35; 95% confidence interval 0.24-0.53) and the tendency to fatal recurrence (not significantly) greater (0.11 events/100 person-years vs 0.07 events/100 person-years) than in the remaining patients. Major bleeding occurred in 5 (1.3%) patients. The case fatality rate for bleeding was 14.3%.During 5-year AT, 30% of patients dies, 10% experiences recurrences, and 5% has fatal recurrences. According to guidelines, most patients need to continue AT; the case fatality rate for bleeding is lower than that for recurrence.