Background: Research on unimanual tasks suggested that motor asymmetries between hands may be reduced in people with Down syndrome. Our study examined handedness (as assessed by hand performance) and perceptual-motor integration effects on bimanual coordination. Methods: Adults with Down syndrome (13 non-right-handed, 22 right-handed), along with comparison groups of adults (16 non-right-handed, 21 right-handed) and children (15 non-right-handed, 22 right-handed) without Down syndrome, drummed with auditory, verbal and visual instructions. Results: In contrast to handedness effects in the children and adults without Down syndrome, right-handed participants with Down syndrome led more with the left hand, and had lower coordination stability than non-right-handed participants with Down syndrome. Conclusions: The reversed handedness effect during bimanual coordination suggests a complex relationship between handedness and task requirements in adults with Down syndrome.