BACKGROUND Cigarette smoking is associated with worse symptoms in asthma and abnormal segmental airways in healthy subjects. We tested the hypothesis that current symptom control in smokers with asthma is associated with altered segmental airway dimensions measured by CT scan. METHODS In 93 subjects with mild, moderate, and severe asthma (smokers and never smokers), we recorded Asthma Control Questionnaire-6 (ACQ-6) score, spirometry (FEV 1 ; forced expiratory flow rate, midexpiratory phase [FEF 25%-75% ]), residual volume (RV), total lung capacity (TLC), and CT scan measures of the right bronchial (RB) and left bronchial (LB) segmental airway dimensions (wall thickness, mm; lumen area, mm 2 ) in the RB3/LB3, RB6/LB6, and RB10/LB10 (smaller) airways. RESULTS The CT scan segmental airway (RB10 and LB10) lumen area was reduced in smokers with asthma compared with never smokers with asthma; RB10, 16.6 mm 2 (interquartile range, 12.4-19.2 mm 2 ) vs 19.6 mm 2 (14.7-24.2 mm 2 ) ( P = .01); LB10, 14.8 mm 2 (12.1-19.0 mm 2 ) vs 19.9 mm 2 (14.5-25.0 mm 2 ) ( P = .003), particularly in severe disease, with no differences in wall thickness or in larger airway (RB3 and LB3) dimensions. In smokers with asthma, a reduced lumen area in fifth-generation airways (RB10 or LB10) was associated with poor symptom control (higher ACQ-6 score) (−0.463 [−0.666 to −0.196], P = .001, and −0.401 [−0.619 to −0.126], P = .007, respectively) and reduced postbronchodilator FEF 25%-75% (0.521 [0.292-0.694], P P = .001, respectively) and higher RV/TLC %. CONCLUSIONS The CT scan segmental airway lumen area is reduced in smokers with asthma compared with never smokers with asthma, particularly in severe disease, and is associated with worse current symptom control and small airway dysfunction.