Excess body weight is associated with an imbalance between energy expenditure and dietary intake but evidence on the association between diet quality and body composition remains equivocal. Rather than relying on differences in diet quality between overweight/obese and normal weight adults, this study examined the association between the Healthy Eating Index 2010 (HEI-2010) and body fatness on a continuous scale, independent of physical activity (PA). Further the association between components of the HEI-2010 and risk for overweight/obesity was explored. 407 adults (27.6 6 3.7 years) provided at least two 24-hour diet recalls over a period of 14 days, which were used to calculate the HEI-2010. Percent body fat (BF) was assessed via dual X-ray absorptiometry and PA was determined via a multi-sensor device, worn over a period of 10 days. PA was a stronger contributor to the variability in BF than the HEI-2010 and the association between HEI-2010 and BF was significant only in men. Particularly a high consumption of protein, sodium and empty calories increased the risk for overweight/obesity. Adherence to dietary guidelines positively affects body fatness in men, independent of PA. In contrast to current dietary recommendations, the risk for overweight/obesity was increased with a higher protein intake.