Objectives: The objective was to report on the initial measurement properties of the Pediatric Quality of Life Inventory™ (PedsQL™) Spinal Cord Injury (SCI) Module in youth with SCI from the youth and parent perspectives. Methods: PedsQL™ SCI Module and PedsQL™ 4.0 Generic Core Scales SF15 were completed in a multisite national study by 166 youth ages 8 to 25 years and 128 parents of youth ages 5 to 23 years. Data from the PedsQL™ Generic Core Scales were compared with an age- and sex-matched healthy control sample. Factor analysis was conducted to determine the factor structure of the items. Results: In addition to a Total Scale Score, nine unidimensional scales were derived measuring daily activities, mobility, bladder function, bowel function, pressure injury, pain interference, social participation, worry bladder bowel, and worry social. The PedsQL™ SCI Module evidenced excellent reliability for Total Scale Scores (youth self-report, α = 0.93; parent proxy-report, α = 0.93) and acceptable reliability for the nine individual scales (youth self-report, α = 0.71–0.83; parent proxy-report, α = 0.67–0.87). Intercorrelations with the Generic Core Scales supported construct validity with medium to large effect sizes (most ps < .001). Factor analysis supported the unidimensionality of the nine individual scales. PedsQL™ Generic Core Scales comparisons to healthy controls demonstrated significantly impaired generic health-related quality of life in youth with SCI with large effect sizes. Conclusion: The PedsQL™ SCI Module Scales demonstrated acceptable measurement properties and may be utilized as standardized scales to assess SCI-specific concerns and problems in clinical research and practice in youth with SCI.