Objective To explore the mechanical ventilation in ICU patients with respiratory failure with pulmonary hypertension plasma brain natriuretic peptide (BNP) levels. Methods 50 patients needed mechanical ventilation with respiratory failure and pulmonary hypertension were randomly divided into two groups (each n = 25). On the basis of routine therapy, patients in noninvasive mechanical ventilation group received assistant breathing masks, and those in invasive mechanical ventilation group received tracheotomy or tracheal intubation. Blood gas analysis, plasma BNP levels, and pulmonary artery pressure before and 24 h after treatment were recorded. Results The arterial blood gas analysis index in the two groups 24 h after treatment were significantly improved (P < 0.05), especially in invasive mechanical ventilation group, so as the results of plasma BNP levels and pulmonary artery pressure (P < 0.05). Conclusions Invasive mechanical ventilation for ICU patients with respiratory failure and pulmonary hypertension is relatively better than noninvasive mechanical ventilation treatment. BNP concentration can be decreased by Mechanical ventilation, especially by invasive mechanical ventilation.