Background: Bevacizumab in combination with chemotherapy increases progression-free survival (PFS) but not overall survival (OS) when compared to chemotherapy alone in the treatment of metastatic breast cancer (MBC). Recently, the United States Food and Drug Administration announced it would withdraw its approval of bevacizumab in breast cancer because its benefits did not outweigh its “significant risks”. The European Medicines Agency, in contrast, maintained its approval of bevacizumab in combination with paclitaxel, but not with docetaxel or capecitabine. While neither agency considers health economics in their decision-making process, one of the greatest challenges in the practice of oncology today is to reconcile hard-won small incremental clinical benefits with exponentially rising costs. Methods: In order to inform policy-makers in the US, this study aimed to assess the cost-effectiveness of bevacizumab plus paclitaxel in MBC, from a payer perspective. We created a decision-analytical model using efficacy and adverse events data from the ECOG 2100 trial. Health utilities were derived from available literature. Costs were obtained from the Center for Medicare Services Drug Payment Table and Physician Fee Schedule and are represented in 2010 US dollars. Quality-adjusted life years (QALY) and Incremental Cost Effectiveness Ratio (ICER) were calculated. Sensitivity analyses were performed. Results: Bevacizumab added 0.49 years of PFS and 0.135 QALY with an incremental cost of $100,300 and therefore a cost of $204,000 per year of PFS gained and an ICER of $745,000 per QALY. The main drivers of the model were drug acquisition cost, PFS, and health utility values. Using a threshold of $150,000/QALY, drug price would have to be reduced by nearly 80% or alternatively PFS increased by 10 months to make bevacizumab cost-effective. The results of the model were robust in sensitivity analyses. Conclusions: The addition of Bevacizumab to paclitaxel is not cost-effective in the treatment of metastatic breast cancer. Value-based pricing and the development of biomarkers to improve patient selection are needed to better define the role of the drug in this population.