Background: Hypoxemia during the induction of general anesthesia for the morbidly obese patient is a major concern of anesthesiologists. The etiology of this pathophysiological problem is multifactorial, and patient positioning may be a contributing factor. The present study was designed to identify optimal patient positioning for the induction of general anesthesia that minimizes the risk of hypoxemia in these patients. Methods: 26 morbidly obese patients (body mass index - BMI 56±3) were randomly assigned to one of three positions for induction of anesthesia: 1) 30° Reverse Trendelenburg; 2) Supine-Horizontal; 3) 30° Back Up Fowler. Mask ventilation, full neuromuscular paralysis and direct laryngoscopy were performed. Any airway difficulties were noted. After endotracheal tube placement, subjects were ventilated for 5 minutes with 1% isoflurane in a mixture of 50% oxygen /50% air and then disconnected from the ventilation circuit. The time required for capillary oxygen saturation (SaO2), as measured by pulse oximeter, to decline from 100% to 92% was noted and identified as the safe apnea period (SAP). Ventilation was then immediately re-established. The lowest SaO2 after resuming ventilation and the time from that nadir to an SaO2 of 97% were also recorded. Results: BMI and hip-waist ratios of patients in groups 1, 2 and 3 did not significantly differ. There were no differences in airway difficulties between the different groups. The SAP in groups 1, 2 and 3 was 178±55, 123±24 and 153±63 seconds, respectively. The SaO2 of patients in the reverse Trendelenburg position dropped the least and took the shortest time to recover to 97%. Conclusions: In morbidly obese patients, the 30° Reverse Trendelenburg position provided the longest SAP when compared to the 30° Back Up Fowler and Horizontal-Supine positions. Since on induction of general anesthesia morbidly obese patients may be difficult to mask ventilate and/or intubate, this extra time may preclude adverse sequelae resulting from hypoxemia. Therefore, Reverse Trendelenburg is recommended as the optimal position for induction.