Tehran University of Medical Sciences Journal of Biostatistics and Epidemiology 2383-4196 10 1 2024 12 01 124 131 Mahboobeh Taherizadeh 1Department of Biostatistics, Faculty of Health, Mashhad University of Medical Sciences, Mashhad, Iran. Mohammad Shakeri 1Department of Biostatistics, Faculty of Health, Mashhad University of Medical Sciences, Mashhad, Iran. Saeed Akhlaghi 1Department of Biostatistics, Faculty of Health, Mashhad University of Medical Sciences, Mashhad, Iran. Ehsan Mosa Farkhani 2Department of Epidemiology, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran. 3Social Determinants of Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 2024 06 24 2024 08 17 Objective: To estimate the effectiveness of two-dose COVID-19 vaccination in reducing hospitalization, accounting for complex confounding factors in observational studies. Methods: Researchers applied propensity score methods to adjust for confounding variables, comparing their performance to traditional covariate adjustment methods. Multiple Logistic Regression and Propensity Score Matching were employed to analyze the data, ensuring a balanced comparison between vaccinated and unvaccinated groups. Results: Both analytical methods demonstrated a significant reduction in the likelihood of hospitalization among vaccinated individuals. The adjusted odds ratios (OR) were 0.29 (95% CI: 0.26, 0.31) via logistic regression and 0.32 (95% CI: 0.30, 0.34) using propensity score matching. Conclusions: The study confirms the effectiveness of two-dose COVID-19 vaccination in decreasing hospitalization. It highlights the importance of using meticulous approaches like propensity score methods to assess real-world impacts in complex observational data settings. https://jbe.tums.ac.ir/index.php/jbe/article/view/1464