Since COVID-19 risk of reinfection is of great concern, the safety and efficacy of the mRNA-based vaccines in previously infected populations should be assessed. We studied 78 individuals previously infected with SARS-CoV-19, who received a single dose of BNT162b2 mRNA COVID-19 vaccine, and 1:2 ratio matched infection-naïve cohort who received two injections. The evaluation procedure included symptom monitoring, and serological tests. Among the post-infected population, the median IgG-S response after the first vaccine dose was 3.35 AU, compared to 2.38 AU after the second vaccine injection in the infection naive group. A strong correlation was demonstrated between IgG-S level before vaccination, and the corresponding responses after a single vaccine dose (r = 0.8, p < 0.001) in the post infected population. Short-term severe symptoms that required medical attention were found in 6.8% among the post-infected individuals, while none were found in the infection naïve population. Our data suggest that a single vaccine dose is sufficient to induce an intense immune response in post-infected population regardless of seropositivity. Although some short-term safety issues were observed compared to the infection naïve population, a single dose regimen can be considered safe in post-infected populations.