Objectives: To determine whether the improved clinical status after newborn screening (NBS) for cystic fibrosis (CF) segregates with increased therapeutic intervention compared with presentation by clinical diagnosis (CD). Study design: In 2002, two populations (1 to 9 years of age) who presented (excluding meconium ileus) by NBS ≤ 3 months of age or by CD were compared in an observational, cross-sectional design. NBS and CD populations (184 and 950 patients, respectively) were divided into 3-year age groups (1 to 3, 4 to 6, and 7 to 9 years)-. Therapies of duration >3 months were compared together with Pseudomonas aeruginosa infection status. Results: NBS patients≤ 6 years of age received significantly fewer and less demanding therapies not explained by age, genotype, geography, or social deprivation. In 7-to 9-year-olds, significantly fewer NBS patients received intravenous antibiotics. NBS patients without P aeruginosa infection received significantly fewer therapies, but no differences were found between intermittently or chronically infected NBS and CD populations. Comparable results were found in Δ F508/Δ F508 subpopulations. Conclusions: CF populations diagnosed by NBS are associated with reduced treatment compared with age and genotype-matched CD control subjects. Objectives: To determine whether the improved clinical status after newborn screening (NBS) for cystic fibrosis (CF) segregates with increased therapeutic intervention compared with presentation by clinical diagnosis (CD). Study design: In 2002, two populations (1 to 9 years of NBS and CD populations (184 and 950 patients, respectively) were divided into 3-year age groups (excluding meconium ileus) by NBS ≤ 3 months of age or by CD were compared in an observational, cross-sectional design. Therapies of duration> 3 months were compared together with Pseudomonas aeruginosa infection status. Results: NBS patients ≤ 6 years of age received significantly fewer and less demanding therapies not explained by age, genotype, geography, or social deprivation. In 7-to 9-year-olds, significantly fewer NBS patients received intravenous antibiotics. NBS patients without P aeruginosa infection received significantly fewer therapies, but no dif ferences were found intermittently or chronically infected in NBS and CD populations. Comparable results were found in Δ F508 / Δ F508 subpopulations. Conclusions: CF populations diagnosed by NBS are associated with reduced treatment compared with age and genotype-matched CD control subjects.