BACKGROUND The present study intends to describe the characteristics of patients diagnosed with severe alpha-1 antitrypsin deficiency (AATD) in Spain, to observe the rate of decline in forced expiratory volume in 1 second (FEV1) with and without substitutive therapy, and to identify factors associated with a rapid rate of decline in FEV1. METHODS A retrospective study of the evolution of individuals with AATD was carried out based on data collected from the Spanish registry. The primary response variable was the annual rate of decline in FEV1, calculated using the baseline and last postbronchodilator FEV1 values in an endpoint analysis. RESULTS 303 patients with severe AATD and Pi ZZ phenotype were identified. Follow-up spirometric data were collected for 117 subjects. Being a smoker or ex-smoker versus never smoker (odds ratio [OR]=10.31; 95% confidence interval (CI)=1.8-58.8; p=0.008) and having a higher baseline postbronchodilator FEV1 (% predicted) (OR=1.03; 95% CI=1.005-1.06; p=0.018) were independently associated with a more rapid rate of decline in FEV1. There was also a trend towards a relationship between low body mass index (BMI) and a greater rate of deterioration in lung function (OR=1.14; 95% CI=0.98-1.33; p=0.085). CONCLUSIONS Being a smoker or ex-smoker, greater baseline lung function, and low BMI were the main risk factors associated with an accelerated rate of decline in FEV1. This finding warrants the close observation of younger patients with a better-preserved FEV1.