To examine the association of genotype with smoking and other key health behaviors among individuals with alpha-1 antitrypsin deficiency (AATD) associated lung disease. Self-reported data were analyzed from 3506 individuals with AATD-associated lung disease. All data were collected upon enrollment in a disease management program designed for individuals who have been prescribed augmentation therapy. Multivariate logistic regression was utilized to examine the extent to which genotype was associated with smoking and other key health behaviors (i.e., getting a pneumonia vaccine, getting a flu vaccine, exercising, and maintaining a healthy weight). We hypothesized that MZs and SZs are more likely than ZZs to be current smokers, and that genotype is associated with additional health behaviors. MZs and SZs had higher odds of being a current smoker than ZZs (MZ versus ZZ OR = 2.73, p < .001; SZ versus ZZ OR = 4.34, p < .001). For every additional health behavior examined, MZs had higher odds of unhealthy behavior than ZZs (ORs ranged from 1.35 to 1.98, p < .05). SZs had higher odds of unhealthy behavior than ZZs with regard to lack of exercise (OR = 1.52, p = .003) and failure to maintain a healthy weight (underweight OR = 1.93, p = .028; overweight OR = 1.43, p = .015). Among individuals who have been prescribed augmentation therapy for lung disease due to AATD, genotype is associated with smoking and additional health behaviors that are central to managing lung disease.