Invasive meningococcal disease (IMD) is under-reported in countries that do not employ polymerase-chain reaction for surveillance because culture-negative cases are omitted. To evaluate a clinically based, case-finding method, we developed case definitions for “probable,” “compatible with,” and “possible, but unlikely” IMD, respectively, based on supportive documentation (e.g., discharge diagnosis of meningococcal infection, culture-negative bacterial meningitis, petechiae/purpura, Gram-negative diplococci on Gram stain) and weight of clinical evidence, which we then applied to electronic health records for all children aged ≤5 y who were admitted to approximately 100 US hospitals between January 2000 and June 2009. Among 47,863 qualifying admissions, 16 children had culture-positive IMD, 5 had “probable” IMD and 5 had illness “compatible with” IMD. Five additional children had disease considered “possible but unlikely” IMD. Our case-finding methods suggest that culture-based ascertainment may underestimate the number of IMD cases by 31–63%, supporting findings in other nations that culture-based reporting provides incomplete information on disease incidence and therefore underestimates the potential benefits of routine vaccination of young children against meningococcal disease.