Objectives <p>This hospital-based study evaluated the magnitude and characteristics of musculoskeletal anomalies in children with Down syndrome.</p> Methods <p>Children aged 3&#xa0;months to 14&#xa0;years, diagnosed to have Down syndrome by karyotyping, were evaluated for musculoskeletal anomalies. We excluded children diagnosed with another chronic condition affecting musculoskeletal health (e.g., cerebral palsy, muscular diseases); and those with any acute illness, which is likely to affect evaluation for musculoskeletal anomalies. A detailed history was taken,&#xa0;and clinical examination was performed by a pediatrician and an orthopedic surgeon. Detailed joint examination was done using pGALS (pediatric Gait Arms Legs and Spine), and Beighton Hypermobility Score was used to assess hypermobility in those aged 6&#xa0;year or more. <i>X</i>-ray cervical spine (lateral view in neutral, flexion and extension) was done for all children to determine atlantoaxial instability. Additionally, in children with any suspected musculoskeletal anomaly on clinical examination, relevant radiological investigations were performed under the guidance of an orthopedic surgeon.</p> Results <p>The median (IQR) age of the study population (<i>n</i> = 75) was 5 (2.5, 8) years with 56% boys. Musculoskeletal anomalies were identified in 86.6%&#xa0;(<i>n</i> = 65). Hypotonia and joint laxity (77.3% each) were common in the whole group; pes planus (82%) and orthopedic abnormalities (69.3%) were prevalent among ambulatory children. Occurrence of genu valgum was found to increase with increasing body mass index (<i>P</i> = 0.045).</p> Conclusions <p>Musculoskeletal problems were common in children with Down syndrome, and this information&#xa0;may guide health professionals in early identification of musculoskeletal problems in children with Down syndrome.</p>