Experimental evidence indicates that leptin-deficient animals develop left ventricular (LV) hypertrophy, but data relating circulating leptin levels to cardiac structure and function in subjects >70 years old are lacking. We related circulating leptin concentrations to echocardiographic measurements of cardiac structure and function in 432 participants of the community-based Framingham Heart Study (mean age 75 years, 67% women) who underwent echocardiography at a routine examination (approximately 4 years before leptin concentrations were assayed). In multivariable linear regression, logarithmically transformed gender-standardized leptin concentrations were related to the following echocardiographic measurements: LV mass, left atrial size, and fractional shortening (primary analysis); LV wall thickness and LV end-diastolic dimensions (the 2 components of LV mass); and transmitral early/late diastolic filling velocities (secondary analysis). Leptin concentrations were inversely associated with LV mass, LV wall thickness, and left atrial size (p <0.04 for all). The top gender-specific tertile of leptin was associated with an adjusted LV mass 16 g lower compared with the lowest tertile (p = 0.007 for trend across tertiles). Leptin levels were not associated with LV fractional shortening, transmitral early/late diastolic filling velocities, or LV end-diastolic diameter (p >0.16). In conclusion, our cross-sectional observations suggest a cardioprotective influence of leptin on LV remodeling consistent with experimental data and may provide insight into the potential role of leptin resistance as a mediator of obesity-associated cardiomyopathy.