Long-term care facilities (LTCFs) were severely affected by COVID-19, in particular in Northern Italy. We aimed to assess antibody responses among residents and healthcare workers (HCWs) of 13 LTCFs through serum samples collected at three time points: prior to, two weeks, and 9 months after receiving Pfizer/BNT162b2 SARS-CoV-2 mRNA vaccine (respectively t0, t1, and t2). IgG antibodies targeted towards the S1 domain of the spike protein were measured, and results were expressed in binding antibody units (BAU/mL). Friedman’s average rank test was performed to compare antibody titres between the three time points. Two logistic regression models were built to identify independent predictors of (1) developing and (2) maintaining a significant antibody response to vaccination, using a previously identified threshold. In total, 534 subjects were enrolled (371 HCWs and 163 residents). The antibody titres at t1 were the highest; at t2, the IgG titres significantly decreased, remaining however 10 times higher compared to titres at t0. Previous infection was the only significant predictor of developing and maintaining a response over threshold in both models. Results of this study provided further insights on the humoral response elicited by vaccination, and on host factors determining variations in its magnitude and kinetics.