In patients receiving anticoagulant therapy for venous thromboembolism (VTE), the important issue of anemia influence on the risk of bleeding has not been consistently studied. We used the large registry data RIETE (Registro Informatizado Enfermedad Tromboembólica) to compare the rate of major bleeding in patients receiving anticoagulant therapy for VTE according to the presence or absence of anemia at baseline. Patients with or without cancer were separately studied. Until August 2016, 63492 patients had been enrolled. Of these, 21652 (34%) had anemia and 14312 (23%) had cancer. Anemia was found in 57% of the patients with cancer and in 28% without (odds ratio 3.46; 95% CI 3.33-3.60). During the course of anticoagulant therapy, 680 patients with cancer had a major bleeding event (gastrointestinal tract 43%, intracranial 14%, hematoma 12%). Cancer patients with anemia had a higher rate of major bleeding (rate ratio [RR]: 2.52; 95% CI 2.14-2.97) and fatal bleeding (RR 2.73; 95% CI 1.95-3.86) than those without anemia. During the course of anticoagulation, 1133 patients without cancer had major bleeding (gastrointestinal tract 32%, hematoma 24%, intracranial 21%). Patients with anemia had a higher rate of major bleeding (RR 2.84; 95% CI 2.52-2.39) and fatal bleeding (RR 2.76; 95% CI 2.07-3.67) than those without. On a multivariable analysis, anemia independently predicted the risk for major bleeding in patients with and without cancer (hazard ratios: 1.66; 95% CI 1.40-1.96 and 1.95; 95% CI 1.72-2.20, respectively). During anticoagulation for VTE, both cancer- and non-cancer anemic patients had a higher risk for major bleeding than those without anemia. In anemic patients (with or without cancer), the rate of major bleeding during the course of anticoagulant therapy exceeded the rate of VTE recurrences. In patients without anemia the rate of major bleeding was lower than the rate of VTE recurrences.