A study was undertaken to describe the practice and outcomes of mechanical ventilation throughout Korea. This prospective cohort study was conducted over a three-month period enrolling patients (n = 519) who received mechanical ventilation for more than 72 hours in 21 university hospital intensive care units throughout Korea. The most common indication for mechanical ventilation was acute respiratory failure. The most common cause of acute-on-chronic respiratory failure was tuberculous lung disease. The most common initial mode for ventilation was volume-controlled ventilation. The mean tidal volume of acute respiratory distress syndrome patients was 7.6 ml/kg of the predicted body weight and the mean positive end-expiratory pressure was 9.4 cmH20. The weaning success rate at 28 days was 50.3%. Pressure support and the T-piece were most commonly used as initial and final weaning modes respectively. Preventive measures against deep vein thrombosis during mechanical ventilation were performed more frequently in intensive care units with full-time critical care physicians than those without such physicians. Multivariate analysis showed that the APACHE II score, indication for mechanical ventilation, respiratory rate at 72 hours, enteral feeding and prophylaxis of deep vein thrombosis were prognostic factors for survival. In Korean intensive care units, tuberculous lung disease remains an important cause for mechanical ventilation. The practice of mechanical ventilation in Korean intensive care units in general appeared to comply with the current international recommendations with regard to lung protection and weaning. However, intensive care units lacking critical care physicians seemed to be adopting fewer ancillary measures, such as deep vein thrombosis prophylaxis.