The aim of this study was to retrospectively evaluate the factors associated with mortality before the age of 30 in adults with cystic fibrosis (CF) followed up at a referral center in southern Brazil. This study included individuals over 18 years of age. Clinical data related to childhood and the period of transition to an adult healthcare of individuals with CF were recorded, as well as spirometric and mortality data of individuals between 18 and 30 years of age. A total of 48 patients were included in this study, of which 28 (58.3%) were male. Comparing groups, we observed a higher prevalence of homozygosis for the F508del mutation (P=0.028), massive hemoptysis before the age of 18 (P=0.027), and lower values of pulmonary function, forced expiratory volume in the first second (FEV1) (%) (P=0.002), forced vital capacity (FVC) (%) (P=0.01), and FEV1/FVC (%) (P=0.001) in the group that died before age 30. F508del homozygosis, episodes of massive hemoptysis in childhood, and lower FEV1 values at age 18 were related to mortality before age 30 in a cohort of individuals with CF in southern Brazil.