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• Osteocalcin plays a protective role in insulin resistance and obesity. • Osteocalcin levels were independently and inversely correlated with prolonged QTc interval after adjusting for confounding factors among a community-based population. • VFA partially mediated the inverse correlation between osteocalcin levels and QTc interval. Osteocalcin, a bone-derived factor, could be a feasible marker for metabolic disorders and adverse cardiovascular outcomes. This study aimed to explore the correlation between serum osteocalcin levels and correct QT interval (QTc) interval prolongation, a risk factor of cardiac morbidity and mortality. We recruited 1210 subjects (age range: 26–80 years) in communities in Shanghai. Serum osteocalcin levels were determined using an electrochemiluminescence immunoassay. The QTc interval was measured using a 12-lead electrocardiogram and was calculated by the Bazett formula. A prolonged QTc interval was defined as QTc > 440 ms. Visceral fat area (VFA) was assessed by magnetic resonance imaging. A VFA of 80 cm2 was applied as a cut-off point for central obesity. Subjects with diabetes, overweight/obesity, or central obesity had significantly lower serum osteocalcin levels than those without (all P < 0.01). In subjects with a normal QTc interval, QTc interval lengthening accompanied decreasing osteocalcin levels (P for trend = 0.033), and the decline was more obvious in subjects with a prolonged QTc interval (P for trend = 0.022). Serum osteocalcin levels were correlated with the QTc interval (standardized β = –0.082, P = 0.005). Neither diabetes nor overweight/obesity was correlated with the QTc interval, whereas central obesity was positively correlated (P = 0.032). In addition, the correlation between osteocalcin levels and the QTc interval was attenuated when central obesity was included in the model simultaneously (standardized β = –0.075, P = 0.010). Mediation analysis revealed that VFA played a mediating role in the aforementioned correlation, and the estimated percentage of the total effect mediated by VFA was 20.9% (P = 0.007). VFA partially mediated the inverse correlation between the serum osteocalcin levels and QTc interval, suggesting that improving fat metabolism may be a mechanism by which osteocalcin protects against cardiovascular diseases. [ABSTRACT FROM AUTHOR]