<i>Objectives:</i> Platinum compounds are commonly associated with significant anemia. Erythropoietin administration has been found effective in correcting anemia in patients with solid tumors receiving chemotherapy. We conducted a randomized, open label study to assess the efficacy of erythropoietin in preventing transfusions and significant anemia (hemoglobin <10 g/dl) in patients with solid tumors receiving platinum-based chemotherapy. <i>Methods:</i> One hundred forty-four patients with hemoglobin <13 g/dl were included in this study (72 in each arm). Patients in the treatment arm received 10,000 U of recombinant human erythropoietin (rHuEPO) thrice weekly s.c. during platinum-based chemotherapy, while patients in the control arm received no treatment. <i>Results:</i> All patients were evaluable for efficacy. Transfusions were reduced by the administration of rHuEPO (15.3 vs. 33.3%, p = 0.019), and fewer patients developed significant anemia (16.6 vs. 45.8%, p < 0.0001). Subgroup analysis showed that patients with observed to predicted (O/P) serum erythropoietin levels ≤0.9 and responders to chemotherapy benefited from erythropoietin administration in contrast to patients with O/P >0.9 or non-responders. <i>Conclusions:</i> rHuEPO at a dose of 10,000 U thrice weekly prevents transfusions and development of significant anemia in patients with solid tumors receiving platinum-based chemotherapy.