Serum leucine-rich alpha-2 glycoprotein (LRG) and calprotectin have been studied as disease activity markers in adults with inflammatory bowel disease (IBD). We evaluated them in pediatric IBD patients. Subjects under 17years old undergoing care at 11 Japanese pediatric centers were retrospectively assigned to 3 groups representing Crohn's disease (CD), ulcerative colitis (UC), and normal controls (NC) with irritable bowel syndrome or no illness. Serum LRG and calprotectin were measured using commercial enzyme-linked immunosorbent assay kits. We enrolled 173 subjects, including 74 with CD, 77 with UC, and 22 NC. Serum LRG concentrations in active CD (median, 200μg/mL) were significantly greater than in remission (81μg/mL; P<0.001) or NC (69μg/mL; P<0.001). Serum calprotectin concentrations in active CD (2941ng/mL) also were significantly greater than in remission (962ng/mL; P<0.05) or NC (872ng/mL; P<0.05). Serum LRG concentrations in active UC (134μg/mL) were significantly greater than in remission (65μg/mL; P<0.01) but not significantly greater than in NC (69μg/mL); serum calprotectin concentrations in active UC (1058ng/mL) were not significantly different from those in remission (671ng/mL) or NC (872ng/mL). In receiver operating characteristic analyses of LRG, calprotectin, C-reactive protein, and erythrocyte sedimentation rate for ability to distinguish active IBD from remission, CD and UC showed areas under receiver operating characteristic curves for LRG (0.77 and 0.70, respectively), exceeding those for calprotectin, C-reactive protein, or erythrocyte sedimentation rate. In pediatric IBD, serum LRG may better reflect disease activity than serum calprotectin, particularly in CD.