Introduction: Mortality rate of breast cancer has been fallen in recent years. Combination of cyclophosphamide, methotrexate, and 5-fluorouracil(CMF), as a pioneer of adjuvant chemotherapy of breast cancer, and later introduced anthracycline/taxane(A/T)-based regimens have both produced favorable outcomes in early-stage breast cancer. The current study, aimed to evaluate the probably different outcomes between CMF and A/T regimens.Methods: In this cohort study, we extracted medical records of 1098 breast cancer patients referred to some oncology centers of Mashhad University of Medical Sciences from 1370 to 1390. Invasive cancers on stages I and II candidate for systemic chemotherapy were included. We categorized patients in the CMF and A/T arms and considered median event free survival (EFS), median overall survival (OS), 5- and 10-year EFS, and 5- and 10-year OS as the endpoints of the study.Results: In the CMF arm, median EFS was 190 months and the 5 and 10-year EFS were 77% and 61% respectively, while in the A/T arm, median EFS was 212 months and 5 and 10-year EFS were 74% and <61% respectively, without significant difference between two arms (P= 0.3). The 5 and 10-year OS were 87% and 76% in the CMF arm respectively, and 83% and <76% in the A/T arm respectively (p=0.2).Stage and estrogen receptor (ER) status significantly affected outcome in univariate analysis, however, the only important prognostic factor in multivariate analysis was the disease stage.Conclusion: Similar effectiveness exists between CMF and A/T-based regimens regarding outcomes of adjuvant treatment for early-stage breast cancer. We could be confident that CMF is more favorable due to infrequent side effects.