Background: Treatment for metastatic breast cancer (MBC) that is not concordant with the NCCN Guidelines for Breast Cancer has been associated with higher healthcare utilization and payer costs. However, a significant knowledge gap exists regarding the impact of guideline-discordant care on patient cost responsibility. This study examined this question among patients withMBC in the year postdiagnosis. Methods: This retrospective cohort study used data from the SEER-Medicare linked database from 2000 through 2013. Guideline discordance, defined by year-specific NCCN Guidelines, was assessed for first-line antineoplastic treatment and grouped into discrete categories. Patient cost responsibility (deductibles, coinsurance, copayments) in women with MBC were summed for all medical care received in the year postdiagnosis. The difference in patient cost responsibility by guideline discordance status was estimated using linear mixed-effect models. Results: Of 3,709 patients with MBC surviving at least 1 year postdiagnosis, 17.6% (n5651) received guideline-discordant treatment. Median cost responsibility in the year postdiagnosis for patients receiving guideline-discordant treatment was $7,421 (interquartile range [IQR], $4,359-$12,983) versus $5,171 (IQR, $3,006-$8,483) for those receiving guidelineconcordant care. In adjusted models, guideline-discordant treatment was significantly associated with $1,841 higher patient costs in the first year from index diagnosis date (95% CI, $1,280-$2,401) compared with guideline-concordant care. Patient cost responsibility differed by category of guideline discordance, with those receiving nonapproved bevacizumab having the highest cost responsibility (b5$3,330; 95% CI, $1,711-$4,948). Conclusions: Deviations from current treatment guidelines may have implications on patient healthcare cost responsibility. Additional research is needed to fully understand the mechanisms underlying how guideline deviation leads to greater costs for patients with MBC.