Earlier cross-sectional studies found that a single magnetic resonance imaging (MRI) slice predicts total visceral and subcutaneous adipose tissue (VAT and SAT) volumes well. We sought to investigate the accuracy of trunk single slice imaging in estimating changes of total VAT and SAT volume in 123 overweight and obese subjects who were enrolled in a 24-week CB-1R inverse agonist clinical trial (weight change, -7.7 ± 5.3 kg; SAT change, -5.4 ± 4.9 l, VAT change, -0.8 ± 1.0 l). VAT and SAT volumes at baseline and 24 weeks were derived from whole-body MRI images. The VAT area 5-10 cm above L(4)-L(5) (A(+5-10)) (R(2) = 0.59-0.70, P < 0.001) best predicted changes in VAT volume but the strength of these correlations was significantly lower than those at baseline (R(2) = 0.85-0.90, P < 0.001). Furthermore, the L(4)-L(5) slice poorly predicted VAT volume changes (R(2) = 0.24-0.29, P < 0.001). Studies will require 44-69% more subjects if (A(+5-10)) is used and 243-320% more subjects if the L(4)-L(5) slice is used for equivalent power of multislice total volume measurements of VAT changes. Similarly, single slice imaging predicts SAT loss less well than cross-sectional SAT (R(2) = 0.31-0.49 vs. R(2) = 0.52-0.68, P < 0.05). Results were the same when examined in men and women separately. A single MRI slice 5-10 cm above L(4)-L(5) is more powerful than the traditionally used L(4)-L(5) slice in detecting VAT changes, but in general single slice imaging poorly predicts VAT and SAT changes during weight loss. For certain study designs, multislice imaging may be more cost-effective than single slice imaging in detecting changes for VAT and SAT.