We sought to describe the clinical features and outcomes of therapy-related chronic myelomonocytic leukemia (t-CMML) and compare with those of de novo CMML. We identified 358 CMML patients, of whom 39 (11%) had t-CMML. Although the groups had similar demographic, hematologic, and molecular alteration profiles, the proportion of patients with intermediate or high CMML-specific cytogenetic risk in the t-CMML was significantly higher than that in the de novo CMML (P = .011). The median latency to develop t-CMML was 6 years. The median overall and leukemia-free survival duration of the t-CMML were shorter than those of the de novo CMML; however, t-CMML itself was not prognostic after adjusting for the effects of other covariates including cytogenetics. These results suggest that compared with de novo CMML, t-CMML is associated with more high-risk cytogenetics that manifest as poor outcomes. We propose that t-CMML be recognized as one of the therapy-related myeloid neoplasms.