INTRODUCTION: Ventilator-associated pneumonia (VAP) is difficult to diagnose. Recent data suggest quantitative endotracheal aspirate (ETA) may be noninferior diagnostically to quantitative bronchoalveolar lavage (BAL). We hypothesized this would be the case. METHODS: Blind quantitative ETA and BAL were performed on 150 consecutive ventilated patients with suspected VAP in a prospective single-centre medical intensive care unit study over a 2-year inclusion period. Patients were either antibiotic-naive or antibiotic-free for 72 hours. Diagnostic yield, Gram stain and culture results, and impact on antibiotic therapy were assessed. The independent impact of a positive BAL or ETA result on ventilator settings and 28-day mortality was calculated. The BAL/ETA safety was assessed hemodynamically. RESULTS: Bronchoalveolar lavage had significantly higher diagnostic yield (49.3% vs 34.0%, P = .01), more frequent impact on antibiotic therapy (usually de-escalation) (48.0% vs 32.7%, P = .01), and greater sensitivity (64.1% vs 42.6%, P = .0003) than ETA. There was moderate intertest agreement and no difference in specificity and positive and negative predictive values. A positive BAL or ETA result did not independently alter the frequency of ventilator changes or 28-day mortality. Both procedures were well tolerated. CONCLUSION: Quantitative BAL is safe and has greater diagnostic utility than ETA for VAP facilitates de-escalation. This study provides support for quantitative BAL in VAP diagnosis.