Background: The NeoSphere trial (Gianni et al. [2012]) compared the following regimens for neoadjuvant treatment in HER2+, locally advanced, inflammatory or early breast cancer: 1) trastuzumab and docetaxel (TH) 2) pertuzumab, trastuzumab and docetaxel (THP), 3) pertuzumab plus trastuzumab (HP), and 4) pertuzumab plus docetaxel (TP). The pathological complete response (pCR) rates were 29.0% for TH, 45.8% for THP, 16.8% for HP, and 24.0% for TP. THP significantly increased the pCR rate. We performed a cost-effectiveness analysis of THP compared to other treatment regimens in the neoadjuvant setting based on the pCR results from NeoSphere. Methods: We constructed a combined decision-analytic (decision tree) and partitioned survival (area under the curve) model with three health states: disease-free (DF), progressive disease (PD), and death. The decision tree modeled the probability of pCR and the partitioned survival model projected life expectancy of patients who did or did not achieve pCR. Utility data for health states were assigned to calculate quality-adjusted life years (QALYs). We estimated the cost of early breast cancer systemic therapy, drug administration, drug monitoring, clinical management of adverse events, and progressive disease (PD). We performed univariate and probabilistic sensitivity analyses. Results: See Table. The incremental cost-effectiveness ratios (ICERs) comparing THP to TH were $34,700/LY and $38,500/QALY, THP to HP, $33,000/LY and $36,900/QALY, and THP to TP, $16,100/LY and $17,800/QALY. The ICERs (THP vs. TH) were most sensitive to pCR difference between THP and TH and the cost of pertuzumab. Conclusions: Pertuzumab combined with trastuzumab and docetaxel is projected to be cost-effective in the neoadjuvant setting. This study suggests that this regimen, in addition to being clinically effective, would be favorable from an economic standpoint in the U.S.