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Although it is clear that ventilated intensive care unit (ICU) patients have worse outcomes than those who are not, information about the risk factors of in-hospital mortality remains important for medical groups to target interventions for these patients.The purpose of this study was to identify predictive factors of in-hospital mortality in ventilated ICU patients with an admission diagnosis of acute respiratory failure.We conducted a prospective cohort study in 3 medical ICUs in a 3600-bed university hospital. Consecutive patients with acute respiratory failure who received mechanical ventilation (MV) for at least 96 hours without evidence of pre-existing neuromuscular diseases were followed until discharge. Upon inclusion, the following parameters were collected or evaluated: demographics, clinical history (admission body mass index [BMI], etiology of acute respiratory failure, comorbidity, Charlson comorbidity index, laboratory data), Acute Physiology and Chronic Health Evaluation (APACHE) II, and right and left quadriceps femoris muscle force. The days of MV before extubation, ICU length of stay, survival status at discharge, and hospital length of stay were recorded from the hospital discharge summary. The primary endpoint was in-hospital mortality.In all, 113 patients (65.49% males) were recruited with a mean age of 69.78 years and mean APACHE II score of 22.63. The mean ICU length of stay was 14.88 ± 9.79 days. Overall in-hospital mortality was 25.66% (29 out of 113 patients). Multivariate analysis showed that the essential factors associated with increased in-hospital mortality were lower BMI (P = .013), and lower scores on the right or left quadriceps femoris muscle force (P = .002 and .010, respectively).Our study suggests that lower BMI and lower scores on lower limb muscle force may be associated with increased in-hospital mortality in ventilated ICU patients.