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/m 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.