Obstructive sleep apnea (OSA) is traditionally diagnosed using overnight polysomnography. Decision rules may provide an alternative to polysomnography. A consecutive series of patients referred to a tertiary sleep center underwent prospective evaluation with the upper airway physical examination protocol, followed by determination of the respiratory disturbance index using a portable monitor. Seventy-five patients were evaluated with the upper airway physical examination protocol. Historic predictors included age, snoring, witnessed apneas, and hypertension. Physical examination-based predictors included body mass index, neck circumference, mandibular protrusion, thyro-rami distance, sterno-mental distance, sterno-mental displacement, thyro-mental displacement, cricomental space, pharyngeal grade, Sampsoon-Young classification, and over-bite. A decision rule was developed using three predictors: a cricomental space of 1.5 cm or less, a pharyngeal grade of more than II, and the presence of overbite. In patients with all three predictors (17%), the decision rule had a positive predictive value of 95% (95% confidence interval [CI], 75-100%) and a negative predictive value of 49% (95% CI, 35-63%). A cricomental space of more than 1.5 cm (27% of patients) excluded OSA (negative predictive value of 100%, 95% CI, 75-100%). Comparable performance was obtained in a validation sample of 50 patients referred for diagnostic testing. This decision rule provides a simple, reliable, and accurate method of identifying a subset patients with, and perhaps more importantly, without OSA.