In patients of various ages undergoing mechanical ventilation (MV), it has been observed that positions other than the standard supine position, such as the prone position, may improve respiratory parameters. The benefits of these positions have not been clearly defined for critically ill newborns receiving MV.This is an update of a review first published in 2005 and last updated in 2013. Primary objectiveTo assess the effects of different positioning of newborn infants receiving MV (supine vs prone, lateral decubitus or quarter turn from prone) in improving short-term respiratory outcomes. Secondary objectiveTo assess the effects of different positioning of newborn infants receiving MV on mortality and neuromotor and developmental outcomes over the long term, and on other complications of prematurity. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8), MEDLINE via PubMed (1966 to 22 August 2016), Embase (1980 to 22 August 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 22 August 2016). We also searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised and quasi-randomised clinical trials comparing different positions in newborns receiving mechanical ventilation. Three unblinded review authors independently assessed trials for inclusion in the review and extracted study data. We used standard methodological procedures as expected by The Cochrane Collaboration and assessed the quality of the evidence using the GRADE approach. If the meta-analysis was not appropriate owing to substantial clinical heterogeneity between trials, we presented review findings in narrative format. We included in this review 19 trials involving 516 participants. Seven of the included studies (N = 222) had not been evaluated in the previous review. Investigators compared several positions: prone versus supine, prone alternant versus supine, prone versus lateral right, lateral right versus supine, lateral left versus supine, lateral alternant versus supine, lateral right versus lateral left, quarter turn from prone versus supine, quarter turn from prone versus prone and good lung dependent versus good lung uppermost.Apart from two studies that compared lateral alternant versus supine, one comparing lateral right versus supine and two comparing prone or prone alternant versus the supine position, all included studies had a cross-over design. In five studies, infants were ventilated with continuous positive airway pressure (CPAP); in the other studies, infants were treated with conventional ventilation (CV).Risks of bias did not differ substantially for different comparisons and outcomes. This update detects a moderate to high grade of inconsistency, similar to previous versions. However, for the analysed outcomes, the direction of effect was the same in all studies. Therefore, we consider that this inconsistency had little effect on the conclusions of the meta-analysis. When comparing prone versus supine position, we observed an increase in arterial oxygen tension (PO2) in the prone position (mean difference (MD) 5.49 mmHg, 95% confidence interval (CI) 2.92 to 8.05 mmHg; three trials; 116 participants; I2= 0). When percent haemoglobin oxygen saturation was measured with pulse oximetry (SpO2), improvement in the prone position was between 1.13% and 3.24% (typical effect based on nine trials with 154 participants; I2= 89%). The subgroup ventilated with CPAP (three trials; 59 participants) showed a trend towards improving SpO2 in the prone position compared with the supine position, although the mean difference (1.91%) was not significant (95% CI -1.14 to 4.97) and heterogeneity was extreme (I2= 95%).Sensitivity analyses restricted to studies with low risk of selection bias showed homogeneous results and verified a small but significant effect (MD 0.64, 95% CI 0.26 to 1.02; four trials; 92 participants; I2= 0).We also noted a slight improvement in the number of episodes of desaturation; it was not possible to establish whether this effect continued once the intervention was stopped. Investigators studied few adverse effects from the interventions in sufficient detail. Two studies analysed tracheal cultures of neonates after five days on MV, reporting lower bacterial colonisation in the alternating lateral position than in the supine posture. Other effects - positive or negative - cannot be excluded in light of the relatively small numbers of neonates studied. This update of our last review in 2013 supports previous conclusions. Evidence of low to moderate quality favours the prone position for slightly improved oxygenation in neonates undergoing mechanical ventilation. However, we found no evidence to suggest that particular body positions during mechanical ventilation of the neonate are effective in producing sustained and clinically relevant improvement.