Chemotherapy-induced nausea/vomiting (CINV) is a major problem for patients treated with high-dose chemotherapy (HDCT) conditioning before stem cell transplantation (SCT), both during chemotherapy and afterwards (delayed nausea/vomiting). The standard of care (5-HT3 antagonist and dexamethasone) appears to be ineffective against delayed nausea and vomiting. The objective of this study was to compare standard antiemetic treatment with standard treatment plus prolonged treatment with aprepitant (Emend®) until 7 days after the end of chemotherapy in patients treated with HDCT before autologous SCT. Ninety-six patients were randomized to the experiment (EXP) group receiving Emend in addition to standard antiemetics or to the control (CTR) group receiving placebo. Emend or placebo treatment started 1 h before the first HDCT dose for SCT and ended 7 days after HDCT. Thirty-eight patients in the EXP group experienced complete response (no vomiting) compared to 16 patients in the CTR group. There was a significant difference between the EXP (0.63 ± 2.71) and the CTR (3.72 ± 4.91) group during 10 days after the end of HDCT (p = 0.001) with regard to the number of vomiting episodes. No difference with regard to days of nausea or in the use of antiemetic rescue was noted between the groups. We conclude that standard antiemetic treatment can be improved by addition of aprepitant continued for 7 days after the end of chemotherapy.