Introduction: A major goal in the management of patients with chronic lung illness is enhancing their quality of life (QoL). Data regarding this issue in patients with alpha-1 antitrypsin deficiency (AATD) is virtually nonexistent. Objective: To analyse the impact of gender, functional parameters, augmentation therapy and number of hospitalizations (previous year) with health-related QoL (HRQoL) in AATD patients. Methods: Twenty-six adult patients with AAT deficient alleles (phenotypes ZZ, n=15 and SZ, n=11) were included. Assessment included demographic and clinical data, functional parameters and Portuguese version of the Medical Outcomes Study, Short Form-36 (MOS, SF-36). Results: Twenty-six patients (13 males) with a mean age of 48.23±15.2 years old. Female patients had significantly lower scores in bodily pain (65.2 Vs 89.0, p=0.020), vitality (39.6 Vs 58.8, p=0.048) and mental health (52.9 Vs 74.1, p=0.029). ZZ patients treated with augmentation therapy had higher ranks in change of health item than ZZ patients non treated (p=0.013). A statistically significant positive correlation between FEV1 and physical functioning (r=0.627, p=0.001), role-physical (r=0.434, p=0.030) and general health (r=0.447, p=0.025) was found. There was a statistically significant negative correlation between the number of hospitalizations in the previous year and numerous dimensions of MOS SF-36.Conclusions: In AATD patients, a significant difference between genders was found in the measured HRQoL. Functional parameters, augmentation therapy and number of hospitalizations in the previous year can have an important impact in the HRQoL of AATD patients.