PURPOSE: Home sleep apnea tests are recommended only for patients at high risk of moderate to severe obstructive sleep apnea (OSA, apnea-hypopnea index [AHI] ≥ 15/h). We evaluated 14 factors known to be associated with OSA and identified sex differences in predictors of moderate to severe OSA. METHODS: Retrospective analysis was done on 545 subjects who completed sleep questionnaires and underwent diagnostic polysomnogram at a tertiary sleep center. Univariate and multivariate analysis was conducted separately in males and females to determine which variables were independent predictors of moderate to severe OSA. RESULTS: Overall, physical traits were stronger predictors in both males and females. For each sex, only 3 variables were found to be independently predictive of moderate to severe OSA. In order of predictive strength, this included body mass index (BMI) ≥ 38 kg/m2 (aOR 5.80, p < 0.001), neck circumference (NC) ≥ 17 in. (aOR 2.52, p = 0.002), and Epworth sleepiness scale (ESS) ≥ 13 (aOR 2.22, p = 0.015) for males and age ≥ 50 years (aOR 4.19, p < 0.001), NC ≥ 14.5 in. (aOR 3.13, p = 0.003), and report of morning headaches (aOR 2.00, p = 0.039) for females. Applying the Bonferroni correction, BMI and NC remained significant for males, and age and NC remained significant for females. CONCLUSIONS: In a subject population referred for sleep evaluation at a tertiary care center only a few variables are independently predictive of moderate to severe OSA, and these variables differed between males and females. Only BMI, NC, and a high ESS were independently predictive of moderate to severe OSA in males, whereas age, NC, and morning headaches were independently predictive in females.