The COVID-19 pandemic caused by SARS-CoV-2 has had a profound global impact on public health. This study aimed to evaluate both the clinical characteristics of COVID-19 cases and the efficacy of the vaccination campaign in Tlemcen, Algeria, in 2021. A retrospective analysis was conducted using data from the Public Health Establishment Near Tlemcen (EPSP), University Hospital of Tlemcen. The study included confirmed COVID-19 cases, with clinical evaluations involving PCR testing and chest CT imaging. Among 68,745 confirmed cumulative number of cases, common symptoms included fever, cough, and shortness of breath, while PCR cycle threshold (Ct) values ranged from 15 to 35. CT scans revealed widespread lung involvement, with ground-glass opacities being a predominant feature. Epidemiological trends indicated a steady rise in cases, highlighting sustained transmission and underscoring the importance of diagnostic tools such as PCR and CT imaging in managing disease severity. Parallel to the clinical assessment, a comprehensive analysis of the vaccination campaign was conducted, focusing on vaccine distribution, uptake, and demographic trends. Data for five vaccine brands—Sputnik, AstraZeneca, Sinopharm, Sinovac, and Janssen—were analyzed to assess vaccine distribution efficiency, wastage rates, and demographic uptake patterns. Sinovac emerged as the most widely administered vaccine, accounting for 91.94% of its imported doses, while Sputnik showed the lowest wastage rate, with minimal expired vaccines. Age-specific vaccination trends revealed higher Sinovac uptake among individuals aged 50-64 and 65+, and Janssen was favored by the 30-49 age group. Additionally, individuals with comorbidities showed a stronger vaccine response to Sinovac, suggesting the need for targeted vaccination strategies. These findings provide essential insights into both COVID-19 clinical progression and vaccination dynamics in Tlemcen, contributing to future public health strategies aimed at controlling the spread and impact of COVID-19.