Background: Epoetin theta has arisen as a new option for chemotherapy induced anemia, but no data of its use in clinical practice has been published yet. We assessed the effectiveness and safety of epoetin theta in patients with chemotherapy induced anemia in the clinical practice setting. Methods: This was a multicenter, retrospective, cohort study carried out in adult patients with chemotherapy induced anemia who had received epoetin theta in daily practice at four Spanish hospitals. Hemoglobin response was defined as increased hemoglobin levels ≥ 2 g/dl (complete response) or within 1-2 g/dl (partial response) without blood transfusions within the four weeks previous to blood sampling. Results: Sixty patients were enrolled in the study, and had received a mean of 22,217.8 ± 4,411.6 IU of epoetin theta for a mean of 5.7 ± 5.7 weeks. Mean hemoglobin levels rose from 9.5 ± 1.0 g/dl to 10.4 ± 1.7 g/dl (p < 0.001), with 39 (65.0%) patients showing hemoglobin increases. Sixteen (26.7%) patients achieved complete response at a mean dose of 25,625.0 ± 10,935.4 IU; 13 (21.7%) reached it without dose adjustments, with 10 (76.9%) maintaining an initial dose of 20,000 IU. Fourteen (23.3%) patients achieved partial response at a mean dose of 21,428.6 ± 3,631.4 IU; 13 (21.7%) reached it without dose adjustments, with 12 (92.3%) maintaining an initial dose of 20,000 IU. Sixteen (26.7%) patients received a mean of 1.4 ± 1.1 blood transfusions. One (1.7%) patient reported an epoetin theta-related adverse event (injection site infection); none reported thrombotic events. Conclusions: Epoetin theta was safe and effective in terms of increasing hemoglobin levels and enabled hemoglobin response to be achieved without blood transfusions in daily clinical practice.