Dual-energy X-ray absorptiometry (DXA) provides an important opportunity for estimating total body skeletal muscle (SM) mass from DXA-measured appendicular lean soft tissue (ALST). A DXA SM prediction model was developed with magnetic resonance imaging as the reference and ALST (i. e., sum of arm plus leg lean soft tissue) as a main predictor variable. In the present study we examined whether ALST estimates are comparable across systems (i. e., penciland fan-beam) and manufacturers. Pencil-beam systems (Lunar DPX and DPX-L) are usually considered more accurate but slower than fan-beam systems (Lunar Prodigy and Hologic Delphi A). In this study we compared ALST estimates in 35 healthy adults across these four systems. The methods gave similar group mean (+/-SD) values and were highly intercorrelated. There was no significant bias detected across the four systems. ALST estimates from the evaluated DXA systems are comparable and thus appear interchangeable as methods for quantifying total body SM in vivo.