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The treatment of hip dysplasia in patients with Down syndrome is challenging. We investigated the clinical, functional, and radiographic outcomes of periacetabular osteotomy (PAO) as well as factors associated with its failure at a minimum of 5 years of follow-up.Between 1992 and 2011, 19 patients with Down syndrome (26 hips) underwent PAO at a mean age of 16.2 ± 4.7 years. Hip pain and function were assessed with use of the modified Harris hip score (HHS) and the Gross Motor Function Classification System (GMFCS). The criteria for PAO failure were progression of osteoarthritis with a recommendation for total hip arthroplasty or hip arthrodesis, or an HHS of <60 points. Preoperative and most recent radiographs were assessed for measurement of the lateral and anterior center-edge angles, Tönnis angle, extrusion index, and anterior and posterior wall indices, and for evaluation of the Tönnis grade of osteoarthritis.At an average follow-up of 13.1 ± 5.2 years (range, 5.4 to 24 years), 13 (62%) of 21 hips with an HHS demonstrated good or excellent HHS results (median, 91 points; interquartile range, 65 to 96 points). Ninety-five percent of the patients were independent in ambulation. All radiographic parameters significantly improved after PAO. Eight (31%) of the 26 hips were considered to have failed the procedure. Tönnis grade-2 osteoarthritis (4 hips compared with 1 hip; p = 0.008; odds ratio [OR] = 17.00) and older patient age at the time of the procedure (19.6 ± 6.7 compared with 14.7 ± 2.4 years; p = 0.017; OR = 1.36 per year) were demonstrated to be factors associated with PAO failure in an analysis of hips that failed compared with those without failure at the time of latest follow-up.PAO improves radiographic deformity and helps to preserve independent ambulation in patients with hip dysplasia and Down syndrome. Although nearly 70% of the hips were preserved at an average of 13 years postoperatively, 1 in 3 hips met the criteria for failure, which was associated with older age at the time of the procedure and a moderate osteoarthritis grade (Tönnis grade 2).Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.