Background: Early approval of COVID-19 vaccine has significant benefits for cancer patients treated under the COVID-19 pandemic worldwide. However, there has been limited reports that investigated the safety and efficacy of vaccination in cancer patients and the optimal timing of vaccination during chemotherapy. We therefore investigated the effects of vaccination on treatment in cancer patients receiving chemotherapy. Methods: Our retrospective observational study included 52 patients with gastrointestinal (GI) cancer receiving chemotherapy at the medical hospital of Tokyo Medical and Dental University in Tokyo who had two doses of mRNA COVID-19 vaccine (Pfizer-BioNTech or Moderna) between May 2021 and September 2021. All patients had no history of COVID-19 infection. Treatment- and vaccination-related adverse events were recorded by outpatient interviews and self-reports. All adverse events were evaluated using CTCAE v5.0. Results: Characteristics of patients were as follows (N = 52): median age, 70y (range, 49–89); male/female, 30/22; ECOG PS 0, 75%; local/metastatic, 12/40; mean BMI, 23.4±4.1; comorbidities in 36 (cardiovascular in 24, diabetes in 8, kidney disease in 8, liver disease in 6, lung disease in 1); treatment (cytotoxic in 45, biologics in 23, immune checkpoint inhibitor in 4). Of the 52 patients, 45 received chemotherapy prior to vaccination; days from last dose to first vaccination, median 11 (range, 1–70); days from first to second vaccinations, median 21 (range, 21–41); days from first vaccination to chemotherapy, median 10 (range, 2–34). 11 patients (24.4%) changed treatment schedule: 3 for safety reasons, 4 for myelosuppression and 4 for convenience. 4 patients stopped treatment due to disease progression. Following the first vaccination, 37 patients (82.2%) had adverse events (AEs): injection site pain (n = 35), fatigue (n = 6), fever (n = 3), headache (n = 2), gastrointestinal symptoms (n = 2), redness (n = 1), insomnia (n = 1). There was no treatment- and vaccine-related deaths. Conclusions: Our findings suggest that vaccine-related AEs in GI cancer patients receiving chemotherapy are tolerable, and treatment schedule changes could be minimized. Although careful monitoring is required, COVID-19 vaccination is also recommended for cancer patients toward the convergence of the COVID-19 pandemic.