We aimed to investigate the mechanisms underlying muscle growth after 12 weeks of resistance training performed with blood flow restriction (RT–BFR) and high-intensity resistance training (HRT) in older individuals. Participants were allocated into the following groups: HRT, RT–BFR, or a control group. High-throughput transcriptome sequencing was performed by the Illumina HiSeq 2500 platform. HRT and RT–BFR presented similar increases in the quadriceps femoris cross-sectional area, and few genes were differently expressed between interventions. The small differences in gene expression between interventions suggest that similar mechanisms may underpin training-induced muscle growth.