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The balance between the efficacy and safety of anticoagulant therapy in patients aged >/=90 years with venous thromboembolism (VTE) is uncertain. RIETE is an ongoing, prospective registry of consecutive patients with acute, objectively confirmed, symptomatic VTE. We evaluated the efficacy and safety of anticoagulant therapy during the first three months in all patients aged >/=90 years. In addition, we tried to identify those at a higher risk for VTE. Of 21,873 patients enrolled from March 2001 to February 2008, 610 (2.8%) were aged >/=90 years. Of these, 307 (50%) presented with pulmonary embolism (PE), 240 (39%) had immobility >/=4 days, and 271 (44%) had abnormal creatinine levels. During the first three months of therapy, 140 patients aged >/=90 years (23%) died. Of these, 45 (32%) died of PE (34 of the initial episode, 11 of recurrent PE), 18 (13%) had fatal bleeding. Recent immobility >/=4 days was the most common risk factor for VTE (240 of 610 patients, 39%), but only 54 of them (22%) had received thromboprophylaxis. The most frequent causes for immobility were senile dementia, acute infection, trauma or decompensated heart failure. The duration of immobility was <4 weeks in 126 patients (52%), and most of them were bedridden at home. In conclusion, one in every four VTE patients aged >/=90 years died during the first three months of therapy. Of these, one in every three died of PE, one in every eight had fatal bleeding. Identifying at-risk patients may help to prevent some of these deaths.