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The SYNERGIE study documented the effects on cardiometabolic risk (CMR) indices of a 1-year lifestyle intervention targeting physical activity (PA) and diet followed by a 2-year maintenance period in men with visceral obesity. Improvements in CMR markers and a decrease in low-attenuation muscle (LAM) area were observed after 1 year. Despite a rebound in visceral adipose tissue (VAT) during the maintenance period, insulin resistance (IR) improved. We tested the hypothesis that variations in cardiorespiratory fitness (CRF) and LAM could explain the long-term improvement in IR. A health (<i>n</i> = 88; mean age 49.0 ± 8.2 years) and fitness (<i>n</i> = 72) evaluation was performed at 0, 1, and 3 years. Participants were classified into two groups based on their CRF response over the maintenance period (worsening: CRF− vs. maintenance/improvement: CRF+). During the maintenance period, changes in the psoas and core LAM areas correlated with changes in IR (<i>r</i> = 0.27; <i>p</i> < 0.05 and <i>r</i> = 0.34; <i>p</i> < 0.005) and changes in CRF (<i>r</i> = −0.31; <i>p</i> < 0.01 and <i>r</i> = −0.30; <i>p</i> < 0.05). IR improved in the CRF+ group (<i>p</i> < 0.05) but remained stable in the CRF− group. Men in the CRF+ group regained half of the changes in VAT volume and LAM at the psoas and mid-thigh compared to the CRF− group (<i>p</i> < 0.05). These results support the importance of targeting VAT and CRF/PA for the long-term management of CMR in men with visceral obesity.