Previous studies indicate that serum cystatin C predicts incident heart failure in older adults. Children with chronic kidney disease (CKD) develop left ventricular (LV) diastolic dysfunction, often the initial abnormality of cardiac function. We hypothesized that cystatin C might predict LV diastolic dysfunction in children with CKD. Fifty-seven subjects, aged 6–21 years, with stage 2–4 CKD underwent echocardiography. Diastole was assessed from transmitral Doppler [maximum early (E wave) and late (A wave) diastolic flow velocities (E/A ratio)] and from tissue Doppler [septal mitral annular peak velocities (E′)]. LV filling pressures were determined, using a ratio of E/E′. Fourteen (25%) patients had low E′ and 15 (26%) had high E/E′. Children with abnormal E′ or E/E′ had significantly higher cystatin C levels than children with normal indices (P<0.05). Neither serum creatinine nor measured glomerular filtration rate (GFR) significantly correlated with E’ or E/E’. Stepwise multiple regression analysis showed that cystatin C (β=−0.825, P=0.023) and left ventricular mass (LVM) index (β=0.099, P=0.006) independently predicted E′; LVM index independently predicted E/E′ (β=0.0173, P=0.01). We conclude that, in contrast to measured GFR or serum creatinine level, elevated serum cystatin C might be associated with diastolic dysfunction in children with CKD.