In Lebanon, the nationwide vaccination against COVID-19 was launched in February 2021 using the Pfizer-BioNTech vaccine and prioritizing elderly people, persons with comorbidities, and healthcare workers. Our study aims to estimate the post-introduction vaccine effectiveness (VE) of the Pfizer-BioNTech vaccine in preventing COVID-19 hospitalizations among elderly people ≥75 years old in Lebanon. A case–control study design was used. Case patients were Lebanese, ≥75 years old, and hospitalized with positive PCR results during April–May 2021, and randomly selected from the database of the Epidemiological Surveillance Unit at the Ministry of Public Health (MOPH). Each case patient was matched by age and locality to two controls. The controls were hospitalized, non-COVID-19 patients, randomly selected from the MOPH hospital admission database. VE was calculated for fully (2 doses ≥14 days) and partially vaccinated (≥14 days of the first or within 14 days of the second dose) participants using multivariate logistic regression. A total of 345 case patients and 814 controls were recruited. Half were females, with a mean age of 83 years. A total of 14 case patients (5%) and 143 controls (22%) were fully vaccinated. A bivariate analysis showed a significant association with gender, month of confirmation/hospital admission, general health, chronic medical conditions, main income source, and living arrangement. After adjusting for a month of hospital admission and gender, the multivariate analysis yielded a VE of 82% (95% CI = 69–90%) against COVID-19-associated hospitalizations for those fully vaccinated and 53% (95% CI = 23–71%) for those partially vaccinated. Our study shows that the Pfizer-BioNTech vaccine is effective in reducing the risk for COVID-19-associated hospitalizations of Lebanese elderly people (≥75 years old). Additional studies are warranted to explore VE in reducing hospitalizations for younger age groups, as well as reducing COVID-19 infections.