OBJECTIVES: Chemotherapy-induced nausea and vomiting (CINV) is a significant adverse effect of cancer chemotherapy treatment. The 5-hydroxytryptamine-3 receptor antagonists (5-HT3-RAs), a class of antiemetics, is indicated for the prevention and treatment of CINV. The purpose of this study was to examine the use of rescue antiemetic administration for CINV in patients diagnosed with cancer and undergoing single-day chemotherapy.  METHODS: A retrospective cohort analysis using the Ingenix LabRx® database was conducted. Adult patients diagnosed with lung, breast, or colon cancer, treated with a moderately (MEC) or highly emetogenic chemotherapy (HEC), and who received a prophylactic 5-HT3-RA from 4/1/08 to 3/31/09, were identified. The outcome of interest was the rate of rescue antiemetic administration, per cycle of chemotherapy, between 5-HT3-RA treatment cohorts. Rescue antiemetic utilization was defined by a HCPCS code for administration of an antiemetic from day 2 to the end of the cycle or for 30 days following single-day chemotherapy.  RESULTS  A total of 5,912 patients were identified, 25.7% treated with a HEC regimen and 74.3% on a MEC regimen.The mean age was 56.1 years and 77.1% were female. Patients were treated with a total of 21,821 cycles of chemotherapy.  The most common 5-HT3-RA utilized was palonosetron (73% of cycles) followed by ondansetron (11%), granisetron (10%), and dolasetron (6%). The overall unadjusted rate of rescue antiemetic administration per cycle was 17.6%, and the rate differed by 5-HT3-RA utilized.  Patients treated with palonosetron were significantly less likely to require a rescue antiemetic on a per cycle basis (14.1%), compared to patients treated with another 5-HT3-RA (26.6%), p<.001.  CONCLUSIONS: The results from this retrospective analysis suggest that rescue antiemetic utilization may be significantly reduced in patients undergoing chemotherapy following use of palonosetron vs. another 5-HT3-RA for the prevention of CINV.