OBJECTIVES: Chemotherapy-induced nausea and vomiting (CINV) is a major adverse effect of cancer treatment. The 5-hydroxytryptamine3 receptor antagonists (5-HT3-RA), a class of antiemetic medications, are indicated for the prevention of CINV.  This study compared treatment costs of patients with and without CINV following a highly or moderately emetogenic chemotherapy regimen and antiemetic prevention with a 5-HT3-RA. METHODS: This study was a retrospective cohort analysis using the MarketScan® Medicaid database.  Continuously enrolled adult patients, newly diagnosed with cancer, newly treated with a MEC or HEC regimen, who received a prophylactic 5-HT3-RA during the January 1, 2005 to December 31, 2009, were identified.   The primary outcome of interest was the overall cost of care for patients with and without CINV.  CINV was defined by any claim for nausea and vomiting, fluid depletion or replacement, and the use of a rescue antiemetic during a cycle of chemotherapy. RESULTS: A total of 8812 patients were identified, 33% undergoing HEC and 67% treated with a MEC regimen. The mean age was 56.7 and 65% were female.  Patients were treated with a total of 43,418 cycles of chemotherapy.  The overall rate of CINV was 17% per cycle and the rate differed by prophylactic 5-HT3-RA utilized.  The rate of CINV per cycle for patients treated with palonosetron was 13% compared to 20% for those treated with another 5-HT3-RA.  The average total paid health care cost per cycle was $2827.  Average cost per cycle with and without CINV was $3839 and $2695, respectively, p<0.001. CONCLUSIONS: In this retrospective study, health care costs associated with the prevention of CINV were approximately $1144 per cycle of chemotherapy.  This suggests that a reduction in the rate of CINV for patients undergoing chemotherapy could result in significant health care cost savings in the Medicaid system.  Further studies are warranted to confirm these findings.