OBJECTIVES: Central precocious puberty (CPP) causes premature childhood development of secondary sexual characteristics and accelerated growth and bone maturation. A small body of research links CPP with increased risk for CNS and congenital disorders, but little is known about the association of CPP with other medical conditions. We examined potential associations. METHODS: Seven-year (1997-2004) analysis of Florida Medicaid-enrolled children comparing those aged 3-7 years with precocious puberty (ICD-9 259.1, which may include premature adrenarche) to those without (age-, sex-, race-, year-, disease burden-matched). ICD-9 diagnoses were used to classify disease groups and disease burden (Charlson Index). Fisher's exact test examined differences between groups and logistic regression examined likelihood estimates. RESULTS: Among 720,931 children, 1,644 (0.23%) were diagnosed with CPP. There was a significant difference in disease burden between groups (p<0.0001). After adjustments, compared to Medicaid-enrolled children without the disorder, those with CPP were 6 times more likely to be diagnosed with hemiplegia (OR 6.3, 95% CI 3.8-10.4, p<0.0001); 5 times more likely to be diagnosed with cerebrovascular disease (OR 5.1, 95% CI 3.2-8.1, p<0.0001) or moderate or severe renal disease (OR 4.7, 95% CI 2.2-9.9, p<0.0001); 4 times more likely to be diagnosed with congestive heart failure (OR 3.9, 95% CI 2.1-7.0, p<0.0001), connective tissue disease (OR 3.7, 95% CI 1.4-9.8, p=0.009), or diabetes (OR 3.5, 95% CI 2.0-6.2, p<0.0001); and 3 times more likely to be diagnosed with chronic pulmonary disease (OR 3.1, 95% CI 2.2-4.3, p<0.0001) or AIDS (OR 2.8, 95% CI 1.6-4.9, p=0.0002). CONCLUSION: This is the first large-scale analysis to show an association between ICD-9 claims-based diagnoses of CPP and medical comorbidities. The pathways by which these comorbid conditions may co-occur remain unclear. Given the potential for complex medical comorbidity, patients with CPP may benefit from thorough evaluation for co-occurring medical disorders.