Forty-two consecutive patients with leptospirosis and acute lung injury who were mechanically ventilated were analyzed in a prospective cohort study. Nineteen patients (45%) survived, and 23 (55%) died. Multivariate analysis revealed that 3 variables were independently associated with mortality: hemodynamic disturbance (odds ratio [OR], 6.0; 95% confidence interval [CI], 0.9-38.8; P=. 047), serum creatinine level >265.2 micromol/L (OR, 10.6; 95% CI, 0. 9-123.7; P =.026), and serum potassium level >4.0 mmol/L (OR, 19.9; 95% CI, 1.2-342.8; P=.009). These observations can be used to identify factors associated with mortality early in the course of severe respiratory failure in leptospirosis.