We retrospectively evaluated if personalized Kampo medicine (PKM) could facilitate CTL responses and clinical benefits induced by personalized peptide vaccination (PPV), in which HLA-matched vaccines were selected and administered based on the preexisting host immunity, for advanced esophageal cancer (aEC) patients. Among 34 aEC patients entered in the clinical study, 23 patients received PKM and PPV without (n=12) or with chemotherapy (n=11), while the remaining 11 patients did not receive PKM but received PPV without (n=6) or with chemotherapy (n=5), respectively. Incidence of adverse events was significantly lower or higher in PKM and PPV arm (n=23) or PPV and chemotherapy arm (n=16) as compared to that of the counter arm (n=11 or 18), respectively. Postvaccination PBMCs from the patients undergoing PKM and PPV showed significantly higher CTL responses as compared to the counter arm. The median progression-free survival (PFS) or median survival time (MST) of 34 patients was 2.9 or 7.6 months, respectively. The combination therapy in PPV and PKM arm, but not that in PPV and chemotherapy arm, significantly (P=0.02) prolonged MST. These results could warrant a next step of prospective clinical study of PKM and PPV for aEC patients.