Background: In oncology, many patients receive taxanes as part of their chemotherapy regimens to treat various types of cancers. The most commonly used taxanes, paclitaxel and docetaxel, are known to cause hypersensitivity reactions (HSRs) in 5-10% of cases. Providers at our institution perceived an increase in the frequency of HSR with taxanes after patients received vaccines against COVID-19. We aimed to compare the incidence of HSRs to taxanes among our oncology patients who have or have not received one or more COVID vaccine prior to initiation of either paclitaxel or docetaxel chemotherapy. Methods: Under an IRB-approved protocol, adult patients, ages ≥18, who had initial treatment with one or more infusions of paclitaxel or docetaxel for any type of cancer in 2020 or 2021 at a single cancer institute, were identified. Demographic, clinical and pathologic information was reviewed from electronic medical charts. The primary objective was to compare the rate of HSR reaction to taxanes among patients who had received any vaccine against COVID-19 prior to their initial taxane infusion versus patients who did not receive a COVID vaccine prior to the first taxane infusion. We also aimed to compare the different vaccine types and to describe, if an HSR occurred, if it was at the first or subsequent taxane infusion. Results: In this single-center retrospective cohort study, 355 patients that met the study criteria were analyzed. 204 patients received at least one COVID-19 vaccine prior to their first taxane infusion (58.8% Pfizer-BioNTech, 27.9% Moderna, 13.2% multiple vaccine types) and 151 patients received the vaccine either after their first taxane infusion or were unvaccinated (51.7% Pfizer-BioNTech, 23.8% Moderna, 2.6% Janssen, 21.9% unvaccinated). Of the patients vaccinated for COVID-19 prior to receiving their first taxane infusion, 11.8% had an HSR while 2.6% had an HSR in the post-taxane/unvaccinated group (p 0.003). Severity of HSR reactions was categorized as mild, moderate, or severe based on symptoms. If an HSR occurred, vaccinated patients were more likely to have a worse reaction (p 0.017). Of the 24 patients that had an HSR in the vaccinated group, 14 had a mild reaction, 8 had a moderate reaction, and 2 had a severe reaction. In the post-taxane/unvaccinated group, 3 had a mild reaction and 1 was moderate. 85.7% of HSR to taxanes occurred after the first cycle (24/28 reactions, p <0.001). There was no difference among the vaccine types, though very few patients received the Janssen vaccine. Conclusions: Vaccination for COVID19 prior to initiation of taxane containing chemotherapy was associated with a higher risk of taxane related HSR and a higher risk for more severe reactions. Since vaccination against COVID-19 is highly encouraged, particularly among patients with cancer, it is important for clinicians to be aware of this potential association so that they can better monitor for, and promptly treat these events.