Background <p>Ventilator-associated pneumonia (VAP) is a frequent ICU-acquired infection in critically ill patients undergoing prolonged mechanical ventilation. It is associated with significant morbidity, prolonged hospital stay, and challenges in antimicrobial therapy. This study aimed to identify clinical risk factors, inflammatory markers (C-reactive protein and white blood cell count), and microbial profiles associated with ventilator-associated pneumonia (VAP) in critically ill patients.</p> Methods <p>A retrospective cohort study was conducted including 267 adult ICU patients ventilated &gt; 48&#xa0;h. Demographics, clinical characteristics, ICU practices, laboratory markers, and microbiological profiles were collected. Statistical analysis involved Mann–Whitney U test, chi-square test, correlation analysis, and multivariable binary logistic regression to evaluate predictors of VAP and ICU mortality.</p> Results <p>Of the 267 patients, 222 (83.1%) developed VAP. VAP was significantly associated with prolonged ventilation duration (<i>p</i> = 0.016). Corticosteroid exposure was less frequent among VAP patients (30.4% vs. 50.0%; <i>p</i> = 0.019). In multivariable analysis, higher CRP (adjusted OR [aOR] = 1.29 per unit; 95% CI: 1.14–1.46) and WBC (aOR = 1.23 per unit; 95% CI: 1.09–1.40) independently predicted VAP, whereas ventilation duration was not independently associated (aOR = 0.93 per day; 95% CI: 0.85–1.01). In a mortality model, higher CRP was associated with lower odds of death (aOR = 0.968; 95% CI: 0.941–0.996).</p> Conclusion <p>VAP is highly prevalent in ICU patients requiring prolonged ventilation and is strongly linked with elevated inflammatory markers and multidrug-resistant pathogens. These findings should be interpreted cautiously given the retrospective, single-center design.</p> Clinical trial number <p>not applicable.</p>