Due to advances in care and medical treatment there has been a steady improvement in the life expectancy and quality of life for persons with Down syndrome (DS). It is not known if the increase in longevity will also mean that age‐dependent diseases in a younger generation of adults with DS will occur at a later age. Comparing two generations of adults can give us insight into the different health aspects experienced by adults with DS. Methods: A prospective longitudinal DS study cohort was set up, consisting of participants at a DS outpatient clinic. This clinic provides a yearly multidisciplinary DS Health Watch program. Since its inception, 141 persons have agreed to participate in a longitudinal prospective study, the “Health Watch study.” They visited the outpatient clinic annually from 2007 to 2015, a mean follow‐up of about 5 years (0.1–8.4 years). The mean age of the participants was 33.9 years (18–70 years). Of those, 25% were younger than 20 and 25% were older than 44. Cross‐sectional data were used to compare the generations. Results: Findings are baseline data of this longitudinal “Health Watch study.” The results show a discrepancy in health conditions and functional characteristics between those in the age category of 44 years and older and those below the age of 20 years. Conclusion: This study suggests that differences observed between the generations are possible predictors of a healthier state and longer life expectancy for a younger generation of adults with DS. Only a longitudinal follow‐up can confirm these findings.