AbstractObjectiveTo describe multilevel phenotypes of airway obstruction identified on drug‐induced sleep endoscopy (DISE) in adults.Study DesignRetrospective chart review.SettingTertiary care center.MethodsVideo recordings of DISE on adult patients were retrospectively scored. A cross‐correlation matrix was created to detect significant correlations between DISE findings at anatomical subsites. Three multilevel phenotypes resulted from the matrix: complete collapse at the tongue base with complete collapse at the epiglottis (T2‐E2), complete circumferential obstruction at the velum with complete lateral pharyngeal wall collapse at the oropharynx (V2C‐O2LPW), and incomplete collapse at the velum with complete collapse due to tonsillar hypertrophy (V0/1‐O2T). The mean difference (MD) and 95% confidence interval (CI) were calculated for demographic and polysomnogram metrics of each phenotype compared to all other subjects.ResultsPhenotype 1 (T2‐E2) (n = 88) had older ages (MD 5.784 years, CI [1.992, 9.576]), lower body mass index (BMI) (MD –1.666 kg/m2, CI [02.570, −0.762]), and smaller neck circumferences (MD–0.448 in., CI [−9.14, −0.009]) than the other phenotypes. Phenotype 2 (V2C‐O2LPW) (n = 25) had higher BMIs (MD 2.813 kg/m2, CI [1.362, 4.263]), higher neck circumference (MD 0.714 in., CI [0.004, 1.424]), and higher apnea‐hypopnea index (MD 8.252, CI [0.463, 16.041]). Phenotype 3 (V0/1‐O2T) (n = 20) had younger ages (MD –17.697, CI [−25.215, −11.179]).ConclusionThree distinct multilevel phenotypes of obstruction were identified on DISE, suggesting different anatomic subsites collapse in a nonrandom pattern. The phenotypes appear to represent distinct patient groups and their identification may have implications in terms of pathophysiology and treatment modalities.