Objectives To assess the importance of synchronization of mechanical ventilation with spontaneous respiratory efforts in mechanically ventilated neonates. The actions of this synchronization on ventilation, oxygenation, and BP variation were assessed. Design Prospective evaluation using within-subject comparison of asynchronous and synchronous states. Setting Neonatal ICU in a large, university-affiliated hospital. Patients Fourteen neonates requiring mechanical ventilation who were initially asynchronous with the ventilator. Intervention The ventilator settings were adjusted using the patients' own inspiratory and expiratory timing to create synchronous interaction with the ventilator. Measurements and Main Results Synchrony was assessed using clinical observation combined with inspection of the air flow waveform and computerized analysis of the air flow signal to assess cycle-to-cycle reproducibility, so-called autocorrelation. Synchronous ventilation significantly improved tidal volume (p < .05), minute volume (p < .001), and all indices of the variability of arterial BP (p < .001). Mean airway pressure did not change significantly. No infant developed an air leak syndrome or intraventricular hemorrhage, which have previously been associated with asynchronous ventilation and an unstable BP, respectively. Conclusion Synchronous ventilation can be readily applied to most ventilated neonates. It improves ventilation, and results in a marked reduction in BP variation, which may have implications for reducing the risk of intravestricular hemorrhage. (Crit Care Med 1993; 21:118–124)