BACKGROUND: Several studies proved the effectiveness of Severe Acute Respiratory Syndrome Corona Virus (SARS-CoV-2) vaccines; however, the number of doses and the period between doses that warrant the highest protection remain unclear. This study aims to assess the effectiveness of the Pfizer-BioNTech vaccine and to evaluate the effectiveness of early and delayed second-dose administration of the vaccine. METHODS: This is a retrospective cohort study that was conducted using the data from March 1st, 2021, to August 31st, 2021. Data regarding vaccination coverage and confirmed SARS-CoV-2 infection were obtained using academic hospitals databases and Health Electronic Surveillance Network (HESN) platform. The vaccination status of the participants were categorized as: unvaccinated, vaccinated 1st dose, and vaccinated 2nd dose of Pfizer-BioNTech vaccine. The outcome of interest was positive polymerase chain reaction test for SARS-CoV-2. Generalized linear model with a Poisson distribution was used to estimate the incidence of the infection. FINDINGS: Among 66,775 participants included, 2615 SARS-CoV-2 infections were observed. The sample was relatively young with median age of 22 years and 43% female. A single dose of Pfizer-BioNTech vaccine had 40 % effectiveness. The effectiveness of the vaccine was doubled after the second dose of Pfizer-BioNTech (80 %). The time between the first and the second dose appears to be crucial after observing 75 %, 90 % and 85 % effectiveness with early vaccination, on-time vaccination, and delayed vaccination, respectively. CONCLUSION: For Pfizer-BioNTech vaccine recipients in Saudi Arabia, particularly among a predominantly young population, higher effectiveness against SARS-CoV-2 was observed with two doses of the vaccine. The timing of the second dose appears crucial for the extent of protection against SARS-CoV-2. However, potential residual confounding cannot be discounted, and further studies are needed to validate these findings and improve generalizability.