Background: The NCCN recommends several adjuvant chemotherapies for Her2-negative early stage breast cancer (ESBC) that have shown similar efficacy but lack direct comparisons in randomized clinical trials (RCTs), making the optimal regimen unclear. Regimens of interest include dose dense doxorubicin/cyclophosphamide followed by dose dense paclitaxel (DDACT), q. 3 week doxorubicin/cyclophosphamide followed by weekly paclitaxel (ACWKT), docetaxel/doxorubicin/cyclophosphamide (TAC), docetaxel/cyclophosphamide (TC), and dose dense doxorubicin/cyclophosphamide followed by weekly paclitaxel (DDACWKT). To aid in clinical decision making, we compared the cost-effectiveness of the above regimens to DDACT. Methods: We used a Markov health state transition model to simulate 4 regimens for a cohort with node positive, HER2-negative ESBC over a lifetime. Health states included chemotherapy, disease-free, 1st and 2nd local relapse, distant metastasis and dead. Adverse events (AEs) included febrile neutropenia, congestive heart failure, and leukemia/MDS whose outcomes were derived from RCTs. Efficacy outcomes were taken from a network meta-analysis of 7 RCTs of the above regimens, except DDACWKT, for which efficacy was assumed equivalent to ACWKT and AEs equivalent to DDACT, given the lack of trial data. Health outcomes were measured in terms of quality-adjusted life years (QALYs) and cost-effectiveness (Δcosts/ΔQALYs) compared to DDACT. Quality of life adjustments were based on published health utility weights. Payer perspective costs came from literature. Results: Compared to DDACT, anthracycline-based regimens slightly reduced QALYs and increased costs. By contrast, TC slightly increased QALYs and reduced costs relative to DDACT. Conclusions: This is the first US-based cost-effectiveness analysis of NCCN recommended adjuvant chemotherapy regimens in Her2-negative ESBC. In the proper clinical context, TC is a reasonable choice when comparing QALYs, toxicity, efficacy, and costs compared to the other regimens.