Background: Cancer patients are a vulnerable population to COVID-19. COVID-19 mRNA vaccines have shown to decrease hospitalization and death risk from COVID-19 in cancer patients. Concurrent COVID-19 vaccination and immune checkpoint inhibitors (ICIs) use may impact immune-related adverse events (irAEs) synergistically. Limited data exist on how COVID-19 mRNA vaccines affect irAEs in ICI-treated cancer patients, especially those with breakthrough infections. Methods: We retrospectively analyzed adult patients with malignant solid tumors receiving ICIs at a single cancer institute (January 2020 to July 2021). Fully vaccinated status is defined as two consecutive doses of mRNA vaccines (BNT162b2 and mRNA-1273). Patients who were partially vaccinated, fully vaccinated post COVID-19 infection, vaccinated with non-mRNA COVID-19 vaccines, or last visit within 30 days post vaccination were excluded. All COVID-19 infections were confirmed by PCR. In the vaccinated group, only post-vaccination irAEs were considered as events. Results: 443 patients were included in our study, with 251 (56.7%) vaccinated and 192 (43.3%) unvaccinated. The baseline characteristics were similar between the two groups, except for age (vaccinated median 68 years, unvaccinated median 62 years, p=0.004). With a median follow-up of 12 months, incidences of all-grade irAEs (19.1% vs. 20.3%, p=0.72) and severe irAEs (5.6% vs. 4.2%, p=0.66) were comparable between vaccinated and unvaccinated groups. 34 breakthrough COVID-19 infections occurred. In the vaccinated group, a non-significant trend of higher all-grade irAEs incidence was noted in the COVID-19 infected subgroup compared to uninfected subgroup (29.4% vs. 17.5%, p = 0.11). Univariate analysis linked COVID-19 vaccination (OR 1.54, 95% CI 1.01-2.35, p=0.04) and ipilimumab + nivolumab use (OR 5.57, 95% CI 1.79-17.35, p=0.003) to a higher risk of all-grade irAEs in the entire cohort. After multivariate adjustment, ipilimumab + nivolumab use remained the only variable associated with all-grade irAEs (OR 4.95, 95% CI 1.57-15.64, p=0.006). Conclusions: Our study suggests that COVID-19 mRNA vaccines do not increase irAE risk in cancer patients on ICIs. Fully vaccinated patients with breakthrough COVID-19 infections may safely continue ICI treatment without an increased irAE risk.