Premature lungs are highly susceptible to lung injury induced by chorioamionitis, mechanical ventilation or persistent exposure to high O2 concentrations. The Authors linger on the central role of atelectrauma and volutrauma (by inadequate tidal volume-Vt) in course of mechanical ventilation of preterm infants with RDS. In particular, they evaluate the efficacy and safety of the targeted volume ventilation with the option of the Volume Guarantee (VG). For this reason they present the results of randomized clinical trials in preterm infants (25-32 wks of gestational age) with severe RDS, in mechanical ventilation, without VG or with two different VG (Vt = 3 or 5 ml/Kg). Data collected demonstrate a significative difference (p < 0.05) in terms od reduction of mean airway pressure (PAW), peak inspiratory pressure (PIP) and cytokines production (IL6-IL8 and TNF alfa) in tracheal aspirate fluid in preterm infants in synchronized ventilation with VG set at 5 ml/Kg. These preliminary results seem to demonstrate the protective role of targeted volume ventilation with Vt = 5 ml/Kg (minimal volutrauma with less lung inflammatory response), but without significative reduction of chronic lung disease (CLD) in this group (probably due to multifactorial pathogenesis of CLD).