Background: Chemotherapy-induced nausea and vomiting (CINV) is still one of the major problems in cancer treatment. However detailed profile of CINV in patients with esophageal cancer is not known. Prospective multi-center observational study was conducted to assess the current status of CINV in Japan. Methods: Between May 2011 and December 2012, 193 patients with esophageal cancer who underwent systemic chemotherapy with high (HEC) or moderate emetogenic agents (MEC) were registered. Antiemetic drugs (5-HT₃ receptor antagonists, dexamethasone and NK₁receptor antagonist) were used to suppress CINV. Occurrence and severity of CINV were assessed with a diary provided to the patients prior to chemotherapy. Acute phase (within 24 hours from the start of chemotherapy) and late phase CINV (24 hours or later) were assessed separately. Multivariate logistic regression analysis was conducted to identify the predictive factors for acute and late phase CINV. Results: Of 193 patients 165 were male and 28 were female. Median age was 66 (range 40-84). HEC and MEC were administered in 180 and 13 patients, respectively. Acute phase nausea and vomiting were observed in 9 (4.7%) and 7 (3.6%) of 193 patients, respectively. Late-phase nausea and vomiting were observed in 75 (38.9%) and 18 (9.3%) of 193 patients, respectively. Risk factors for acute phase nausea, acute phase vomiting, late phase nausea and late-phase vomiting were assessed separately. By multivariate analysis for late-phase vomiting, younger age (Odds ratio 0.523 [every 10 years]; 95%CI 0.278-0.986; p=0.045) and male gender (Odds ratio 5.796; 95%CI 1.806-18.603; p=0.003) were independent predictive factors. By multivariate analyses for acute phase nausea, acute phase vomiting and late-phase nausea, no independent predictive factor was identified. Conclusions: Acute phase CINV was effectively suppressed by antiemetic drugs, while late phase CINV was not sufficiently suppressed. Further intervention to suppress late phase CINV should be considered, especially in high-risk patients. Clinical trial information: UMIN000005971.