Abstract We had previously reported short-term efficacy, immunogenicity, and safety of the BNT162b2 vaccine among cancer patients with solid tumors. We aimed to evaluate these outcomes at six months postvaccination. The study cohort comprised patients who were on treatment during vaccination and throughout six months postvaccination. Serologic tests were performed after second vaccination and six months afterward. An age-matched cohort of health care workers served as controls. Documentation of COVID-19 infection, blood tests, and imaging studies during the study period was reviewed. Participants included 154 patients and 135 controls. Six months postvaccination, 122 (79%) patients were seropositive compared with 114 (84%) controls (P = 0.32). Serology titer dramatically decreased in a similar manner in both cohorts. No COVID-19 cases were documented in controls, and one case occurred in patient cohort. All previously reported adverse effects resolved. Taken together, the pattern of immunogenicity, efficacy, and safety of BNT162b2 in patients with cancer with solid tumors at six months postvaccination resembles that of the general population. Significance: Evidence regarding efficacy and safety of COVID-19 vaccines in patients with cancer indicate a favorable short-term profile. Immunomodulation due to anticancer treatments may affect immunity and immunogenicity of patients with cancer to the BNT162b2 vaccine over time. Our study sheds light on these long-term outcomes and portrays a trend that resembles the general population. This article is highlighted in the In This Issue feature, p. 2355