Background: Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the western world. Primarily affecting older patients, CLL increases the risk of infection due to immunosuppression from underlying disease and treatments. With the COVID19 pandemic now in its third year, vaccines remain one of our best protections against infection. However, people with CLL historically have decreased vaccine efficacy; hence protection from the COVID19 vaccines is uncertain. Furthermore, it is unknown if antibodies generated in response to vaccination confer immunity. Therefore, we tested for presence of SARS-CoV-2 antibodies post vaccination to determine if a response was generated and led to a decreased risk of breakthrough infections. Methods: We performed a retrospective cohort study of patients with CLL who received at least one COVID19 vaccine. Spike protein antibodies were assessed in a CLIA-approved laboratory. Detectable spike protein antibodies after vaccination were assessed, excluding those detected any time after Cilgavimab-Tixagevimab administration, within 90 days after any monoclonal antibody or convalescent plasma, or after covid infection post vaccine to best capture antibody responses from the vaccine. Logistic regression model was used to assess the odds of antibody development. Fine-Gray model was used to assess risk of breakthrough infections. Results: 477 patients were included in this study with median age of 60.4 years. Patients were predominately male (64.8%) and white (97.3%). 70.4% of patients had received at least one treatment for CLL. 45.5% of patients were on CLL treatment at time of vaccination, with the majority (87.6%) of these treated with BTK inhibitors either as monotherapy or with a BCL2 inhibitor or anti CD-20 therapy. Three hundred thirteen (68.2%) of the patients had a detectable antibody after vaccination. Those who received CLL treatment were less likely to have detectable antibody response compared to those not on treatment (OR = 0.19, p < 0.0001). Compared with patients who received Moderna vaccine, Pfizer (OR = 0.15, p < .01) and Janssen (OR = 0.46, p = 0.29) vaccine receivers were less likely to have detectable antibodies. Eighty (17.2%) patients developed COVID19 infection after vaccination, with 5% mortality from COVID19. Those who received Pfizer vaccines had a higher risk of infection (HR = 2.25, p = 0.0016). Regardless of vaccine type, those who had antibodies post vaccination had a decreased risk for infection (HR = 0.38, p < 0.0001). Conclusions: Among patients who were vaccinated against COVID19, those who received CLL treatment were less likely to develop antibodies compared to untreated patients, indicating that treatment decreases vaccine efficacy. We show that detectable antibodies after vaccination decrease risk for infection. Moderna appears to have greater efficacy, with more patients having positive antibody titers and a lower risk of developing COVID19.