Although epoetin alfa is commonly used weekly for the treatment of chemotherapy (CT)-induced anemia, most CT is given at three week intervals. Therefore, to provide increased patient convenience we examined a dosing regimen that would allow patients to receive epoetin alfa 80,000 U Q3W during maintenance therapy. This open-label, multi-center study had two phases: Initiation Phase (IP) of 60,000 U QW to achieve target hemoglobin (Hb) of 12 g/dL (maximum duration 12 weeks), followed by a Maintenance Phase (MP) of 80,000 U Q3W to maintain Hb between 11.0 and 12.5 g/dL. Only those patients achieving Hb ≥ 12 g/dL in the IP entered the MP; once target Hb was achieved, patients proceeded to MP at the beginning of their next full CT cycle. Patients were withdrawn from the MP if Hb decreased to < 11 g/dL. Doses were held for Hb > 13 g/dL and reduced for rate of rise > 1.3 g/dL/2 weeks. Maximum study duration (IP + MP) was 24 weeks. Patients ≥ 18 years of age with non-myeloid malignancy, baseline Hb ≤ 11 g/dL, and CT planned Q3W for ≥ 15 weeks were enrolled. Endpoints included proportion of patients achieving hematopoietic response in the IP (≥ 2 g/dL Hb increase from baseline or Hb ≥ 12 g/dL) and proportion maintaining mean Hb between 11.0 and 12.5 g/dL in the MP. Also analyzed was the proportion of patients maintaining mean Hb between 11.0 and 13.0 g/dL in the MP. A total of 115 patients were enrolled and received at least one dose of epoetin alfa; mean age was 62.2 ± 11.9 years, 66.1% were female, mean baseline Hb was 10.2 ± 0.8 g/dL, and 86.1% had solid tumors. During the IP, 84 of 115 (73.0%) patients achieved hematopoietic response (≥ 2 g/dL Hb increase from baseline or Hb ≥ 12 g/dL). Seventy-three patients (63.5%) who achieved Hb ≥ 12 g/dL entered the MP after a median of 6.0 weeks in IP and spent a mean of 9.8 weeks in MP. Fifty-four of 73 (74.0%) maintained an average Hb between 11.0 and 12.5 g/dL over the course of the MP; 64 (87.7%) maintained an average Hb between 11.0 and 13.0 g/dL over the course of the MP. Twenty-five (34.2%) patients were withdrawn from the MP because Hb decreased to < 11 g/dL. Of 115 patients dosed in IP, 30 (26.1%) had doses reduced and 31 (27.0%) had doses held; of 73 patients dosed in MP, 9 (7.8%) had doses reduced and 16 (13.9%) had doses held. Fifty-one (44.3%) patients experienced serious adverse events. Eleven (9.6%) patients experienced clinically relevant thrombotic vascular events. Two and 4 patients discontinued due to adverse events in the IP and MP, respectively. Eight (7.0%) patients died during the study or within 30 days after last study dose. Although 60,000 U QW was used during the IP to achieve a HR, 40,000 U QW is the recommended initiation dose of epoetin alfa. This study suggests that epoetin alfa 80,000 U administered every three weeks to patients on a Q3W CT regimen is an effective option for maintenance therapy of CT-induced anemia.