The primary aim of this study was to evaluate the accuracy of skinfold thickness (SFT) measurements for the estimation of %Fat when compared to dual energy X-ray absorptiometry (DXA) in individuals with Down syndrome (DS). The secondary aim was to develop a new SFT-based body fat equation (SFTNICKERSON). SFT-based %Fat was estimated using a body fat equation from González-Agüero (SFTG-A) and body density conversion formulas from Siri (SFTSIRI) and Brozek (SFTBROZEK). Criterion %Fat was measured via DXA. SFTG-A, SFTSIRI, and SFTBROZEKwere significantly lower than DXA (mean differences ranged from −7.59 to −13.51%; allp< 0.001). The SEE values ranged from 3.47% (SFTBROZEK) to 8.60% (SFTG-A). The 95% limits of agreement were greater than ±10% for all comparisons. Mid-axilla and suprailium were significant predictors of %Fat (bothp< 0.05). %Fat SFTNICKERSON= 10.323 + (0.661 × mid-axilla) + (0.712 × suprailium). Age and all other skinfold sites were not statically significant in the regression model (allp> 0.05). Current findings indicate that SFTG-A, SFTSIRI, and SFTBROZEKerroneously place an individual with excessive adiposity in a normal healthy range. Accordingly, the current study developed a new equation (SFTNICKERSON) that can easily be administered in people with DS in a quick and efficient time frame. However, further research is warranted in this area.