We investigated the antibody kinetics after vaccination against COVID-19 in healthcare workers of a Greek tertiary hospital. Eight hundred and three subjects were included, of whom 758 (94.4%) received the BNT162b2 vaccine (Pfizer-BioNTech), eight (1%) mRNA-1273 (Moderna), 14 (1.7%) ChAdOx1 (Oxford-AstraZeneca) and 23 (2.9%) Ad26.COV2.S (Janssen). Before the second dose, at 2, 6 and 9 months after the second dose and at 2 and 6 months after the third dose, anti-spike IgG were quantified by the chemiluminescence microparticle immunoassay method. One hundred subjects were infected before vaccination (group A), 335 were infected after receiving at least one vaccine dose (group B), while 368 had never been infected (group C). Group A presented a greater number of hospitalizations and reinfections compared to group B (p< 0.05). By multivariate analysis, younger age was associated with an increased risk of reinfection (odds ratio: 0.956,p= 0.004). All subjects showed the highest antibody titers at 2 months after the second and third dose. Group A showed higher antibody titers pre-second dose, which remained elevated 6 months post-second dose compared to groups B and C (p< 0.05). Pre-vaccine infection leads to rapid development of high antibody titer and a slower decline. Vaccination is associated with fewer hospitalizations and fewer reinfections.