OBJECTIVES: CINV with MEC and HEC therapy is well studied, but the association of prior history of CINV with the future risk of CINV is not well quantified. This study assessed the increased likelihood of a subsequent CINV following a first administration CINV in patients on single-day MEC/HEC therapy. METHODS: A retrospective analysis was conducted utilizing Georgia Cancer Specialists electronic medical records database (October 2006 – August 2009).  Patients who received >1 single-day MEC/HEC administration with no chemotherapy 3-months prior were included. Patients who received multiday chemotherapy, started with low emetogenic chemotherapy, or had no dosing information were excluded.  Two cohorts, a first administration CINV (Group 1) and no first administration CINV (Group 2), were created and followed for six months. A multivariate logistic regression assessed the likelihood of subsequent CINV during the six month follow-up, controlling for age, gender, Charlson comorbidity index, cancer type, gap between administrations, and chemotherapy emetogenicity. Sub-analyses were performed for patients initiated on MEC and HEC. RESULTS: A total of 3721 patients met inclusion criteria; 423 (11.37%) experienced a first administration CINV.  These patients were younger (56.6 vs. 59.4; p<0.0001), had lower comorbidity index (2.1 vs. 2.2; p=0.0154) and had more gaps between administrations (18.5 vs. 17.4; p=0.0204).  Unadjusted subsequent CINV rate was higher in the Group 1 cohort (52.3% vs. 24.2%; p<0.0001).  After controlling for covariates, Group 1 patients were 3.5 times more likely to have a subsequent CINV compared to Group 2 patients [Odds Ratio (OR):3.48(95%CI: 2.81-4.30); p<0.0001]. Sub-analyses by MEC/HEC supported overall analysis [HEC OR: 2.9 (95%CI: 2.1-3.9; p<0.0001)] and [MEC OR: 4.1 (95%CI: 3.1-5.5; p<0.0001). CONCLUSIONS: In this retrospective analysis, patients receiving single-day MEC/HEC who had a prior CINV were at increased risk of subsequent CINV. Further research on the clinical and economic impact of early and appropriate anti-emetic prophylaxis is required.