We examined the effects of regular bedside testing of pulmonary mechanics (PM) on the outcome of 468 acutely ill, mechanically ventilated neonates. During the first of two 18-month study periods, 217 infants were mechanically ventilated without the assistance of PM measurements. During the second 18-month period, 251 infants were ventilated with the assistance of at least daily PM measurements. Using data obtained from the PM tests, we adjusted the infants' ventilators to maintain tidal volume, inspiratory time, and pressure-volume loops within predetermined limits. With the exception of the PM measurements, given the limitations of retrospective analyses, both groups of infants received identical medical and nursing care. The infants ventilated with the assistance of PM testing developed fewer pneumothoraces (4.0%; 10/251) vs. no PM testing, 10.1% (22/217); P < 0.05 by Chi-square analysis]. Infants weighing less than 1,500 g ventilated with the assistance of PM measurements had less intraventricular hemorrhage (IVH) overall, most notably, less grades I and II IVH (total IVH-PM testing, 39.1% vs. no PM testing, 65.7%; P < 0.01; Grades I-II IVH-PM testing, 30.4% vs. no PM testing, 54.9%; P < 0.01). IVH incidence was decreased independent of pneumothorax occurrence. Survival rates, incidences of bronchopulmonary dysplasia, and durations of mechanical ventilation and hospitalization were similar. This retrospective analysis suggests that PM testing during infant mechanical ventilation reduces common acute ventilator-associated complications.