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Background: Creatine (Cr) supplementation associated with resistance training produces greater muscular strength improvements in the upper compared with the lower body; however, no study has investigated if such region-specific results are seen with gains in muscle mass.Aim: We aimed to evaluate the effect of Cr supplementation in combination with resistance training on lean soft tissue changes in the upper and lower limbs and trunk in resistance-trained young adult men.Methods: In a randomized, double-blind and placebo-controlled design, 43 resistance-trained men (22.7 ± 3.0 years, 72.9 ± 8.7 kg, 177.9 ± 5.7 cm, 23.0 ± 2.5 kg/m2) received either creatine (Cr, n= 22) or placebo (PLA, n= 21) over an 8-week study period. The supplementation protocol included a loading phase (7 days, four doses of 0.3 g/kg per day) and a maintenance phase (7 weeks, single dose of 0.03 g/kg per day). During the same period, subjects performed resistance training four times per week using the following two-way split routine: Monday and Thursday = pectoral, shoulders, triceps, and abdomen, Tuesday and Friday = back, biceps, thighs, and calves. Lean soft tissue of the upper limbs (ULLST), lower limbs (LLLST), and trunk (TLST) was assessed by dual-energy X-ray absorptiometry before and after the intervention.Results: Both groups showed significant (p< 0.001) improvements in ULLST, LLLST, TLST, and the Cr group achieved greater (p< 0.001) increases in these outcomes compared with PLA. For the Cr group, improvements in ULLST (7.1 ± 2.9%) were higher than those observed in LLLST (3.2 ± 2.1%) and TLST (2.1 ± 2.2%). Otherwise, for PLA group there was no significant difference in the magnitude of segmental muscle hypertrophy (ULLST = 1.6 ± 3.0%; LLLST = 0.7 ± 2.8%; TLST = 0.7 ± 2.8%).Conclusion: Our results suggest that Cr supplementation can positively augment muscle hypertrophy in resistance-trained young adult men, particularly in the upper limbs.