While significant progress has been made in understanding the resistance training (RT) strategy for muscle hypertrophy increase, there remains limited knowledge about its impact on fat mass loss. This study aimed to investigate whether full-body is superior to split-body routine in promoting fat mass loss among well-trained males. Twenty-three participants were randomly assigned to 1 of 2 groups: full-body (n=11, training muscle groups 5days per week) and split-body (n=12, training muscle groups 1day per week). Both groups performed a weekly set volume-matched condition (75 sets/week, 8-12 repetition maximum at 70%-80 % of 1RM) for 8weeks, 5days per week with differences only in the routine. Whole-body and regional fat were assessed using DXA at the beginning and at the end of the study. Full-body RT elicited greater losses compared to split-body in whole-body fat mass (-0.775±1.120kg vs. +0.317±1.260kg; p=0.040), upper-limb fat mass (-0.085±0.118kg vs. +0.066±0.162kg; p=0.019), gynoid fat mass (-0.142±0.230kg vs. +0.123±0.230kg; p=0.012), lower-limb fat mass (-0.197±0.204kg vs. +0.055±0.328kg; p=0.040), and a trend in interaction in android fat mass (-0.116±0.153kg vs. +0.026±0.174kg; p=0.051), with large effects sizes (η2 p≥0.17). This study provides evidence that full-body is more effective in reducing whole-body and regional fat mass compared to split-body routine in well-trained males.