Background Lung ultrasonography (LUS) has been used for noninvasive detection of pulmonary edema. Semiquantitative LUS visual scores (visual LUS V-LUS) based on B lines are moderately correlated with pulmonary capillary wedge pressure (PCWP) and extravascular lung water (EVLW). A new computer-aided quantitative LUS (Q-LUS) analysis has been recently proposed. This study investigated whether Q-LUS better correlates with PCWP and EVLW than V-LUS and to what extent positive end-expiratory pressure (PEEP) affects the assessment of pulmonary edema by Q-LUS or V-LUS. Methods Forty-eight mechanically ventilated patients with PEEP of 5 or 10 cm H2 O and monitored by PCWP (n = 28) or EVLW (n = 20) were studied. Results PCWP was significantly and strongly correlated with Q-LUS gray (Gy) unit value ( r2  = 0.70) but weakly correlated with V-LUS B-line score ( r2  = 0.20). EVLW was significantly and more strongly correlated with Q-LUS Gy unit mean value ( r2  = 0.68) than with V-LUS B-line score ( r2  = 0.34). Q-LUS showed a better diagnostic accuracy than V-LUS for the detection of PCWP >18 mm Hg or EVLW ≥ 10 mL/kg. With 5-cm H2 O PEEP, the correlations with PCWP or EVLW were stronger for Q-LUS than V-LUS. With 10-cm H2 O PEEP, the correlations with PCWP or EVLW were still significant for Q-LUS but insignificant for V-LUS. Interobserver reproducibility was better for Q-LUS than V-LUS. Conclusions Both V-LUS and Q-LUS are acceptable indicators of pulmonary edema in mechanically ventilated patients. However, at high PEEP only Q-LUS provides data that are significantly correlated with PCWP and EVLW. Computer-aided Q-LUS has the advantages of being not only independent of operator perception but also of PEEP.