This cross-sectional study used Geographic Information System methods to compare sociodemographic and clinical characteristics of children enrolled and not enrolled in a primary care network to determine the suitability of the network to estimate population-based disease rates. We validated the network surveillance system by comparing invasive pneumococcal disease rates between network and nonnetwork children using population-based surveillance data. Among the study population of 130300 children, network children were more likely to be female, Black, non-Hispanic, younger, and receive Medicaid. These differences varied across neighborhoods, however, adjusting for neighborhood characteristics did not significantly change observed differences. Rates of invasive pneumococcal disease were not significantly different between network and non-network children. Significant demographic and clinical differences existed between network and non-network children and varied over small areas. Observed population rates of an infectious disease did not significantly differ suggesting that the network can potentially provide valid disease estimates for the community population.