Vitamin K is essential for development of normal bone density and achieving adequate peak bone mass in childhood and is thought to be important in preventing the development of osteoporosis in later life. Warfarin, a vitamin K antagonist, is being used with greater frequency in children. The long-term effect of warfarin on bone density of children is not known. We performed a case control study survey of bone density in children on long-term warfarin (n=17, average duration of warfarin treatment 8.2 y) compared with randomly selected controls (n=321). There was a marked reduction in bone mineral apparent density of lumbar spine between patients and controls [patients 0.10 g/cm3; 95% confidence interval (CI), 0.93-0.11 g/cm3, controls 0.12 g/cm3; 95% CI, 0.11-0.12 g/cm3, p<0.001). The lumbar spine areal bone mineral density Z-score of patients was reduced compared with controls [patients, -1.96 (95% CI, -2.52 to -1.40). This difference persisted after adjustment for age and body size. The etiology for the reduced bone density is likely to be multifactorial, however, screening of children on long-term warfarin for reduced bone density should be considered.