OBJECTIVES: Capecitabine, an oral pro-drug to 5-fluorouracil (5-FU), approved May 2001 for metastatic colorectal cancer (CRC), allows for less invasive, more convenient treatment. However, the cost of oral cancer medications may be prohibitive, affecting their uptake compared to infused alternatives. We investigated uptake and cost of capecitabine over time, including generic capecitabine, approved September 2013. METHODS: We selected patients’ first treatment with capecitabine or 5-FU from MarketScan Commercial data (2002-2014). Patients were ages 18+, had 6 months’ prior medical and pharmacy coverage, a diagnosis of CRC and no prior breast cancer diagnosis. The proportion of patients treated with capecitabine versus 5-FU was calculated by year. Inflation-adjusted cost of index capecitabine fills were calculated annually for branded and generic products. RESULTS: We identified 11,314 capecitabine-treated and 28,502 5-FU-treated patients. Between 2002-2014, capecitabine market share increased from 20% to 34%, with generics accounting for 74% of index capecitabine fills in 2014. The median cost/fill for capecitabine increased from $1,199 to $3,385 from 2002-2013. Median cost of generic fills in 2014 was $2,970, versus $3,232 for brand capecitabine. Out-of-pocket (OOP) cost was <$50 for 85% of patients in 2002, compared to 57% in 2013, while patients paying >$500 rose from <1% to 6%. In 2014, median and mean OOP cost for generic fills were $10 and $61, compared to $40 and $238, respectively, for brand fills. CONCLUSIONS: Uptake of capecitabine as initial fluoropyrimidine therapy for CRC has increased since approval, but most patients still receive 5-FU. Median total cost of capecitabine fills has nearly tripled since 2002. Although generic capecitabine had significant uptake in 2014, the median cost was similar to the branded product, and 2.5 times higher than 2002 branded costs. Mean and median OOP costs for generic products were lower, but OOP costs were <$50/fill for >50% of patients prior to generic entry.