Children with cerebral palsy (CP) and severe hand impairment have limited options for upper extremity (UE) orthoses. To (1) design and fabricate a customized low-cost, functional, three-dimensional (3D) printed dynamic upper extremity orthosis (DUEO) and (2) examine, using a comprehensive evaluation, the effect of the orthosis on the UE function of children with unilateral UE CP, Manual Ability Classification System (MACS) Levels III to V. Pilot study. Assessments were performed pretreatment and immediately posttreatment. Hospital-based outpatient occupational therapy department. Five patients, ages 13 to 17 yr, with CP and unilateral UE involvement MACS Levels III to V. Custom forearm thumb opponens orthosis and the DUEO were designed and fabricated by a multidisciplinary team for use during eight 1-hr occupational therapy sessions targeting bimanual UE training. Pretreatment and posttreatment assessments included the Assisting Hand Assessment (AHA), Melbourne Assessment 2 (MA-2), Pediatric Motor Activity Log-Revised (PMAL-R), and the Pediatric Quality of Life Inventory: CP Module (PedsQL:CP). All participants had higher posttreatment scores on at least one measure. Four had minimal clinically important differences (MCID) on the AHA. Three met MCID criteria on MA-2 subtests (one negative change). Four demonstrated improvement on the PMAL-R (one participant achieved an MCID score), and three reported improvements in more than one PedsQL:CP domain. This novel 3D-printed device, in combination with occupational therapy, shows promising evidence that children who score in lower MACS levels can show gains in UE function. What This Article Adds: This study demonstrates that a customized, 3D-printed dynamic orthosis, in combination with occupational therapy intervention, can facilitate UE function in children with severe hand impairment.