Background: Chemotherapy-induced nausea and vomiting (CINV) is a major adverse toxicity of cancer chemotherapy. Recommended treatments for prevention of CINV vary among guidelines, and optimal care for CINV caused by moderately emetogenic chemotherapy has not been established. This study assess efficacy and safety of triple antiemetic therapy consist palonosetron, dexamethasone and aprepitant for carboplatin-based chemotherapy. Methods: Chemotherapy-naïve patients with lung cancer scheduled for a first course of a carboplatin-containing regimen formed the study cohort. Patients were pretreated with antiemetic therapy consist palonosetron (0.75 mg, i.v.) and dexamethasone (9.9 mg, i.v.) on day 1, and aprepitant (125 mg, p.o.) on day 1 followed by 80 mg on days 2 and 3. Primary endpoint was the proportion of patients who did not experience vomiting and did not require rescue medication (complete response (CR)) in the acute phase (0-24 h), late phase (24-168 h) and overall. Secondary endpoint was the proportion of patients who experienced no vomiting episodes and no more than mild nausea without the need for rescue medication (complete control (CC)). Results: Prevalence of a CR during the acute phase, delayed phase, and overall was 100%, 91.9% and 91.9%, whereas that of CC was 100%, 84.4% and 84.4%, respectively. Most common adverse events were mild constipation; severe adverse events related to antiemetic treatment were not observed. Prevalence of a CR during the acute phase, delayed phase, and overall was 100%, 91.9% and 91.9%, whereas that of CC was 100%, 84.4% and 84.4%, respectively. Most common adverse events were mild constipation; severe adverse events related to antiemetic treatment were not observed. Conclusions: Triple antiemetic therapy comprising palonosetron, dexamethasone and aprepitant shows excellent effects in preventing CINV in patients receiving a carboplatin-containing regimen. Clinical trial information: UMIN000017877.