The incidence of DVT in hospitalized children is increasing. Those presenting with DVT typically have prior DVT, thrombophilia, or lower extremity disease. Our study suggests that children admitted with severe medical conditions who require a prolonged intensive care unit stay in addition to central venous access (especially via the femoral vein) should be considered candidates for DVT prophylaxis. A clinical probability scoring system alone cannot stratify patients sufficiently to forgo prophylaxis in hopes of a rapid clinical diagnosis. Childhood-specific level 1 trials aimed at determining guidelines for DVT prophylaxis are urgently required.