Our aim was to evaluate the influence of static pulmonary compliance (Cst) on the choice of Mechanical Ventilation(MV) method and treatment outcome. A prospective, randomized trial conducted out at the multidisciplinary Intensive Care Unit (ICU) included 387 patients, randomized in two groups: noninvasive MV group and invasive MV group. Furthermore, each group was divided in two groups: Cst < or = 0.025 and Cst > 0.025 L/cm H2O. In patients with Cst > 0.025 L/cm H2O MV duration, noninvasive vs invasive, was 92 vs 114 h, p = 0.039, time spent in ICU 118 vs 164 h, p = 0.004. In patients with Cst < or = 0.025, MV duration was 141 vs 189 h, p < 0.001, time spent in ICU 190 vs 246 h, p = 0.001, all patients were intubated. Need for tracheostomy was 6 (11%) vs 39 (46%) patients, p = 0.005, and ICU mortality was 15 (26%) vs 21 (25%) patients. Statistical significance in favor of noninvasive method was confirmed in patients with Cst > 0.025 L/cm H2O in MV duration, time spent in ICU, need for tracheostomy and intubation rate. In the group with Cst < or = 0.025 no significant difference in treatment failure was recorded between the two MV methods.