Objective: To evaluate the safety and immunogenicity of the Pfizer-BioNTech COVID-19 vaccine in gynecologic oncology patients under chemotherapy. Methods: A prospective cohort study including gynecologic oncology women who were under chemotherapy or had completed it within 6 months at the time of the study. All patients received a two-dose schedule of the Pfizer-BioNTech COVID-19 vaccine. Results were compared with a control group of healthy women vaccinated in the same period. Results: Overall, 44 oncologic patients with a mean age of 61.3 ± 10.7 years were enrolled: 28 (63.6%) had ovarian cancer, 9 (20.4%) endometrial, and 7 (16%) cervical. The IgG antibody titer after 1 month from vaccination was low in 9 (20.5%) patients, moderate in 21 (47.7%), and high in 14 (31.8%). The 3-month titer was null in 2 (4.5%) patients, low in 26 (59.1%), moderate in 13 (29.5%), and high in 3 (6.8%). Patients ≥ 50 years reported lower 1-month (p = 0.018) and 3-month (p = 0.004) titers compared with <50 years. Patients with BMI < 30 kg/m2 had a higher 1-month titer compared with BMI ≥ 30 kg/m2 (p = 0.016). Compared with healthy women (n = 44), oncologic patients showed a lower 3-month titer (p < 0.001). None of the patients experienced serious adverse effects. Conclusions: The COVID-19 vaccine was safe and immunogenic in gynecologic oncology patients under chemotherapy. Serological monitoring and further vaccine shots should be considered to boost protection.