Acute respiratory distress syndrome (ARDS) is a severe respiratory disease with a high mortality rate. It is characterized by acute onset of pulmonary edema, hypoxemia, and the need of mechanical ventilation. As the primary treatment, ventilation has been considered effective in treating patients with ARDS. Recently, numerous studies have shown that prone position ventilation demonstrates more efficacy compared with traditional supine position. However, the potential impact of the non-physiological prone position on patients remains unclear. Current study aims to evaluate the effect of prone position ventilation on right heart function in ARDS patients. Following Berlin Diagnostic Criteria, 80 eligible patients were recruited and randomly assigned into prone position ventilation group and supine position ventilation group. Different ventilation methods were implemented in these two groups. Both positions showed the beneficial effects, as evidenced by decreased PV score and APACHE II score, enhanced blood gas index and right heart function parameters, and the prognosis analysis. However, compared with those receiving SPV treatment, the patients demonstrated greater benefits from PPV treatment, with significant differences in PV score (p < 0.01) and APACHE II score (p < 0.001), blood gas index such as PAPm (p < 0.05), and right heart function indicators (p < 0.05). Prone position mechanical ventilation is more beneficial than supine position ventilation in improving the blood gas status of patients with moderate to severe ARDS, and it is more helpful to reduce the load on the right heart and promote the recovery of patients.