Protocols for chest physiotherapy and suctioning vary among nurseries, and in-line manometers are not used to guide hand-regulated ventilation in all nurseries. We asked whether significant fluctuations in airway pressures occur when hand-regulated ventilation is not guided by manometer readings. Method: Respiratory pressure tracings were recorded in 11 mechanically ventilated neonates during (1) mechanical ventilation, (2) hand-regulated ventilation with in-line manometers, and (3) hand-regulated ventilation without manometric guidance. Results: Positive inspiratory pressures and mean airway pressures were significantly higher (6.46 cm H2O [0.633 kPa], P = 0.00047, and 1.63 cm H2O [0.159 kPa], P = 0.0106, respectively) without in-line manometers. Positive end-expiratory pressures were underestimated, regardless of manometer status. Conclusion: We suggest that in-line manometers be employed routinely for hand-controlled ventilation of neonates to minimize the potential for barotrauma and its consequences.