Contacts of adults with tuberculosis (TB) are at risk for infection. Tests based on interferon-gamma (IFN-gamma) expression in response to Mycobacterium tuberculosis antigens may be more sensitive than the tuberculin skin test (TST). Risk for infection was assessed by using TST and an IFN-y-based assay (QuantiFERON Gold in Tube [QFT-IT] test) for 207 children in Nigeria in 1 of 3 groups: contact with adults with smear-positive TB, contact with adults with smear-negative TB, and controls. For these 3 groups, respectively, TST results were >10 mm for 38 (49%) of 78, 13 (16%) of 83, and 6 (13%) of 46 and QFT-IT positive for 53 (74%) of 72, 8 (10%) of 81, and 4 (10.3%) of 39 (p < 0.01). Most test discrepancies were TST negative; QFT-IT positive if in contact with TB-positive persons; and TST positive, QFT-IT negative if in contact with TB-negative persons or controls. TST may underestimate risk for infection with TB in children.