OBJECTIVES: Phenylketonuria (PKU) is the most common in-born error of metabolism and is associated with neuropsychiatric sequelae. Interviews among adults and parents of children with PKU have established that inattentiveness is an important psychiatric symptom. Although the Adult ADHD Self-Rating Scale (ASRS; self-report) and ADHD Rating Scale (ADHD RS-IV; parent-report) instruments have been validated for measuring symptoms of inattentiveness in persons with ADHD, their psychometric value for measuring PKU-related inattentiveness has not been established. This study investigated the psychometric properties of the ASRS and ADHD RS-IV inattentiveness subscales in a PKU population ≥8 years old. METHODS: A post-hoc analysis was conducted in participants ≥8 years of age in a Phase 3b double blind, placebo-controlled clinical trial in PKU over a 13-week period. The ASRS/ADHD RS-IV reliability, construct validity, and responsiveness were measured using clinician- and adult-/parent-reported outcomes collected in this clinical trial. RESULTS: Data analysis revealed strong internal consistency reliability for both measures (α ≥0.87). In addition, the test-retest analyses resulted in ICCs ≥0.87, indicating outstanding agreement between the Baseline and Week 4 (re-test visit) measures for both the adult- and parent-rated inattentiveness subscales. Both inattentiveness measures demonstrated an ability to discriminate between known groups (p<0.0001) defined by the Clinical Global Impression-Severity (CGI-S) scale. Correlations between the ASRS/ADHD RS-IV with the CGI-S and age-appropriate Behavior Rating Inventory of Executive Function (BRIEF) Working Memory subscale were consistently moderate-to-strong (r ≥0.56). Similarly, results of the change score correlations were moderate (r ≥0.43) for both measures when compared to changes over time in the BRIEF Working Memory subscale. CONCLUSIONS: These findings of reliability, validity, and responsiveness of both the ASRS and the ADHD RS-IV inattentiveness sub-scales, in addition to content validation results, further support their use for the assessment of inattentive symptoms among persons with PKU ≥8 years old in clinical trials.