Background: Patients with primary adrenal insufficiency (PAI) suffer reduced quality of life (QoL), but comparisons with large-scale normative data are scarce. The clinical characteristics associated with reduced QoL are largely unknown. Methods: Cross-sectional data on clinical characteristics and QoL scores from 494 patients were included. QoL was measured using RAND-36 (generic) and AddiQoL (-30 and -8, disease-specific). RAND-36 is reported as subdomain scores as well as physical (PCS) and metal (MCS) summary scores and compared with normative data. Results: Perception of physical role was consistently decreased across age groups in patients with PAI compared with normative data [75 (0-100) vs. 100 (50-100), p<0.001]. Men with PAI reported significantly lower scores for social functioning [88 (75-100) vs. 100 (75-100), p<0.001], as well as for vitality and physical role. In women, the greatest impairment was seen in physical role [50 (0-100) vs. 100 (50-100), p<0.001], followed by social functioning, vitality, physical function, general health, mental health, and emotional role. Overall, better QoL was associated with male sex (AddiQoL-30: 89 ± 13 vs. 82 ± 13, p<0.002), younger age (e.g. 20-29 vs. 80-89 years: PCS 59 [50-62] vs. 46 [37-53], p<0.001), autoimmune etiology [PCS: 53 (45-59) vs.. 45 (38-54), p<0.001], and absence of autoimmune comorbidity [PCS: 54 (45-59) vs. 50 (43-58), p<0.001]. There were no significant differences in QoL scores between different doses or dosing regimens of glucocorticoid or mineralocorticoid replacement. Conclusion: QoL is reduced in patients with PAI, especially perception of physical role in women and social functioning in men. Among patients with PAI, female sex, higher age, non-autoimmune etiology, and autoimmune comorbidity was associated with lower QoL-scores