Objective. The risk of invasive pneumococcal disease is increased among children with some chronic diseases. The objective of this study was to quantify the risk of invasive pneumococcal disease in a wide range of chronic diseases. ATIENTS AND METHODS. Cases of invasive pneumococcal disease among children (aged 0-17 years) were identified from 1977 through 2005 by using a national surveillance program in Denmark. Rate ratios were assessed in a case-control study by using 10 age- and gender-matched controls per case. Chronic diseases were defined a priori. RESULTS. Among 1655 children with invasive pneumococcal disease, 19% had a history of chronic disease, according to our definition, versus 5% of controls. An increased risk of invasive pneumococcal disease was observed for children followed >30 days after initial hospital contact for a chronic disease, but it was also increased in children with ≥5 hospital contacts for any other reason. Children with a history of cancer, chronic renal disease, splenectomy, and transplantation were particularly susceptible to invasive pneumococcal disease. Adjusted for number of hospital contacts, the risk for children with other types of chronic disease was 1.4-fold more than for those with hospital contacts for any reason. CONCLUSIONS. Cancer, chronic renal diseases, splenectomy, and transplantation were strongly associated with an increased risk of invasive pneumococcal disease in children. For children with other chronic diseases, their excess risk seemed to be attributable mostly to frail children having repeated hospital contact rather than their underlying condition.