This study evaluated implant outcome in patients with Down syndrome (DSPs) and provides clinical guidelines to maximize treatment outcome. A total of 57 implants were placed in eight DSPs. During follow-up, implant survival was recorded and crestal bone level was evaluated when possible. After a mean follow-up time of 5 years, six patients with 45 implants were evaluated and an implant survival rate of 84.4% was recorded. A mean crestal bone loss of 1.7 mm (SD 0.9) was measured in three patients around 20 implants. Down syndrome is not a contraindication to dental implant placement, but multiple complicating factors yield reduced implant survival.