Patients initiating highly emetic chemotherapy are at a 90% risk of chemotherapy-induced nausea and vomiting (CINV). Antiemetic drugs are highly effective in preventing CINV and thus improve quality of life and generate cost savings by reducing the need for CINV-related health services. Despite guideline-concordant antiemetic prescribing preventing CINV in up to 80% of patients, evidence suggests that use of ASCO and NCCN guideline-concordant antiemetic regimens by patients initiating highly emetogenic chemotherapy is low. Furthermore, of the multiple CINV preventative treatment regimens that are considered guideline concordant, there is no clear clinical preference and costs vary widely. The purposes of this dissertation were to characterize antiemetic use; identify predictors of antiemetic under-use; and evaluate the trade-offs in cost, clinical, and quality of life outcomes across the guideline-concordant recommendations in patients initiating intravenous highly emetogenic chemotherapy. Aim 1 used descriptive statistics to describe antiemetic prescribing patterns, including antiemetic under-use, in patients with cancer initiating highly emetic chemotherapy using the IBM Watson's/Truven's MarketScan Commercial Claims and Encounters (CCAE) and Medicare Supplemental and Coordination of Benefits data. Aim 2 used a modified Poisson regression to identify factors associated with antiemetic under-use (i.e., environmental, predisposing, enabling, and need) in these same data. Aim 3 assessed the health and economic impacts of guideline-concordant antiemetic strategies through a cost-utility analysis in order to prioritize them. Alarmingly, under-use of guideline-concordant antiemetic fills is high, at 49% and 68% in the commercial claims and Medicare supplement populations, respectively (Aim 1). While more than 75% of patients are filling 5HT3As and dexamethasone, NK1 product fills were low and olanzapine fills were negligible. Site of chemotherapy setting was among the greatest predictors of antiemetic use, with patients receiving chemotherapy in an outpatient hospital setting at a 1.28 (p<0.0001) and 1.48 (p<0.0001) times higher risk of under-use compared to outpatient physician setting in the CCAE and Medicare Supplement populations, respectively (Aim 2). Medical benefit generosity and prescription drug generosity has limited impact on under-use in both populations. Olanzapine + fosaprepitant + 5HT3A + dexamethasone dominates all other strategies; however, after excluding olanzapine-based strategies fosaprepitant + 5HT3A + dexamethasone was the most efficient strategy (Aim 3). Given the limited incremental benefits across strategies, treatment acquisition costs should be considered when deciding on an antiemetic strategy, thus prioritizing first-generation 5HT3As and intravenously administered products.