Background: Prone position (PP) and the positive end-expiratory pressure (PEEP)-induced lung recruitment maneuver (LRM) are both efficient in improving oxygenation and prognosis in patients with ARDS. The synergistic effect of PP combined with PEEP-induced LRM in patients with ARDS remains unclear. We aim to explore the effects of PP combined with PEEP-induced LRM on prognosis in patients with moderate to severe ARDS and the predicting role of lung recruitablity. Methods: Patients with moderate to severe ARDS were consecutively enrolled. The patients were prospectively assigned to either the intervention (PP with PEEP-induced LRM) or control groups (PP). The clinical outcomes, respiratory mechanics, and electric impedance tomography (EIT) monitoring results for the two groups were compared. Lung recruitablity (recruitment-to-inflation ratio: R/I) was measured during the PEEP-induced LRM procedure and was used for predicting the response to LRM. Results: Fifty-eight patients were included in the final analysis, among which 28 patients (48.2%) received PEEP-induced LRM combined with PP. PEEP-induced LRM enhanced the effect of PP by a significant improvement in oxygenation (∆PaO₂/FiO₂ 75.8 mmHg vs. 4.75 mmHg, p < 0.001) and the compliance of respiratory system (∆C_rs, 2 mL/cmH₂O vs. −1 mL/cmH₂O, p = 0.02) among ARDS patients. Based on the EIT measurement, PP combined with PEEP-induced LRM increased the ventilation distribution mainly in the dorsal region (5.0% vs. 2.0%, p = 0.015). The R/I ratio was measured in 28 subjects. The higher R/I ratio was related to greater oxygenation improvement after LRM (Pearson’s r = 0.4; p = 0.034). Conclusions: In patients with moderate to severe ARDS, PEEP-induced LRM combined with PP can improve oxygenation and dorsal ventilation distribution. R/I can be useful to predict responses to LRM.