Dual-energy X-ray absorptiometry (DXA) is widely used for bone mineral density and body composition assessments. However, DXA is known to overestimate muscle mass in obese adults. We used single-slice CT (ssCT) to derive a correction factor to enhance accuracy of DXA estimation of specific strength (strength per unit muscle). One hundred and sixty-two adults (age: 55.0+/-2.7 yr, range: 50-59) were enrolled in this cross-sectional study and divided into groups based on body mass index (BMI: <30, 30-35, and > or =35). BMI groups did not differ in age, knee extensor strength (KES), thigh lean mass by DXA, or quadriceps cross-sectional area (CSA) by ssCT. Specific strength (KES/CSA) correlated with an uncorrected estimate of DXA-specific strength (r = 0.82, 0.53, 0.84 and 0.74, 0.59, 0.57, p < 0.001) in the lowest to highest BMI groups in men and women, respectively. Stronger correlations were achieved through correcting for BMI, age, and sex in estimating DXA-specific strength (r = 0.81, 0.79, and 0.96 in the lowest to highest BMI groups in men and 0.94, 0.81, 0.85 in women, p < 0.0001). Quantification of knee extensor-specific strength by DXA in men with BMI > 30 and all BMI groups in women greatly improved using a correction factor for DXA estimates of thigh lean mass.