Background:The aim of this meta-analysis with trial sequential analysis (TSA) was to evaluate the effect of a polyurethane (PU) tracheal tube cuff on the prevention of ventilator-associated pneumonia (VAP).Methods:We performed a systematic search using the MEDLINE database through PubMed, Cochrane Central Register of Controlled Trial, SCOPUS, and Web of Science.Randomized controlled trials comparing the incidence of VAP and clinically relevant outcomes between PU cuff tubes and polyvinyl chloride (PVC) cuff tubes in adult patients. Two authors independently extracted study details, patient characteristics, and clinical outcomes such as incidence of VAP, bacterial colonization of tracheal aspirate, duration of mechanical ventilation, ICU stay, and ICU mortality.Results:From 309 studies identified as potentially eligible, six studies with 1226 patients were included in this meta-analysis. All studies compared the incidence of VAP between PU cuffs and PVC cuffs. Use of a PU cuff was not associated with a reduction in VAP incidence (RR = 0.68; 95% CI, 0.45–1.03) with significant statistical heterogeneity (I2 = 65%). The quality of evidence was “very low.” According to the TSA, the actual sample size was only 15.8% of the target sample size, and the cumulative Z score did not cross the trial sequential monitoring boundary for benefit. No positive impact was reported for the other relevant outcomes for PU cuffs.Conclusions:The use of a PU cuff for mechanical ventilation did not prevent VAP. Further trials with a low risk of bias need to be performed.