PURPOSE: Studies in the adult’s population have shown an inconsistent association between musculoskeletal fitness (MF) and cardiometabolic risk clustering independent of adiposity. The purpose of this study was two-fold: to analyze the association between MSF and cardiometabolic risk clustering, and to determine the influence of adiposity parameters on the association between MF and cardiometabolic risk clustering in adults from Colombia. METHODS: The cross-sectional study included a total of 886 (51.9% women) healthy children and adolescents. Standing broad-jump and isometric handgrip dynamometry were used as indicators of lower and upper body muscular fitness, respectively. Also, a MF was computed by summing up the standardised values of both standing broad-jump and handgrip strength. We assessed the following adiposity parameters: fat mass, body mass index, waist-to-height ratio and abdominal visceral fat. A MetSyn z-score was calculated for each subject from triglycerides, HDL cholesterol, fasting glucose, waist circumference, and arterial blood pressure (MAP). Linear regression models fitted for mediation analyses examined whether the association between MF and MetSyn z-score was mediated by adiposity parameters according to Baron and Kenny procedures. RESULTS: Findings revealed that lower levels of MetSyn z-score were associated with the best adults profiles (high MF + low adiposity) (p for trend <0.001 in the four adiposity parameters), compared with unfit strength and obese (low MF + high adiposity) counterparts. Linear regression models suggest a full mediation of adiposity parameters in the association of MF with MetSyn z-score, for both men and women alone. CONCLUSIONS: Our findings seem to emphasize the importance of obesity prevention in adults, suggesting that having high levels of MF may not counteract the negative consequences ascribed to adiposity.