Nosocomial infections pose a global health threat, with Ventilator-Associated Pneumonia (VAP) emerging as a prominent hospital-acquired infection, particularly in intensive care units (ICU).VAP is the commonest form of pneumonia in ICUs, contributing significantly to morbidity and mortality rates, which can reach around 30%. Despite the substantial impact of VAP on healthcare, there is a lack of data on adherence to VAP prevention protocols in our hospital. Consequently, this study aims to assess the adherence to ventilator-associated pneumonia care bundles in critical care units at a comprehensive specialized hospital in northwest Ethiopia. A hospital-based prospective observational study was conducted from July 3, 2022, to January 7, 2024. All adult patients who were on mechanical ventilators for more than 48h during the study period were included. Data were collected using the Institute of Healthcare Improvement VAP prevention standards as checklists via direct observation and chart review. The data were entered and analyzed using SPSS version 20. A total of 300 surgical and medical ICU patients were observed. Among the patients, 66.3% were from the medical ICU. In terms of admission reasons, 22.3%, 15.7% and, 12% were attributed to infections excluding respiratory origin, respiratory disorders, and other causes, respectively. The rate of compliance with all components of the bundle was 70%. A 100% adherence rate was observed for the prophylaxis for peptic ulcer and deep vein thrombosis (DVT). The lowest adherence rate was observed in the practice of oral hygiene with 0.5% chlorhexidine solution (0%) followed by humidification with heat and moisture exchangers (23.3%). Endotracheal tube cuff pressure measurement and use of endotracheal tubes with subglottic suction were not applicable. The study revealed suboptimal compliance with the VAP care bundle, indicating unsatisfactory overall practice. Specific attention is warranted for subglottic suction, cuff pressure measurement, humidification, oral care with chlorhexidine, and sedation vacation.