Cardiac disease is a risk factor for venous thromboembolism (VTE) in children. In this study, we investigated the incidence and risk factors of VTE in critically ill children with cardiac disease, who were prospectively followed-up for VTE after admission to a tertiary care pediatric intensive care unit (PICU). Risk factors were compared between VTE cases and (1) patients in the cohort who did not develop VTE and (2) the next three cardiac patients sequentially admitted to the PICU (case control). Forty-one cases of VTE were identified from 1070 admissions (3.8%). Thirty-seven percent of VTE cases were central venous catheter (CVC)-associated, and 56% of cases were intracardiac. Sixty-six percent of patients were receiving anticoagulation at the time of VTE diagnosis. Increased VTE incidence was associated with unscheduled PICU admission, age <6 months, extracorporeal membrane oxygenation, increased number of CVCs, increased number of CVC days, higher risk of mortality score, and longer PICU stay. Using logistic regression, VTE was associated with single-ventricle physiology (odds ratio [OR] 11.2, 95% CI 3.0-41.9), widened arterial-to-somatic oxygen saturation gradient (SpO(2)-rSO(2) >30) (OR 4.3, 95% CI 1.1-16), and more CVC days (OR 1.1, 95% CI 1.04-1.13). Risk factors for VTE in critically ill children with cardiac disease include younger age, single-ventricle cardiac lesions, increased illness severity, unscheduled PICU admission, and complicated hospital course.