OBJECTIVES: Tuberous sclerous complex (TSC) is a multi-system disorder that can affect almost any organ system in the body. The objective of this study is to examine the prevalence and incidence rates of the common co-morbid conditions among patients with TSC. METHODS: We used a large national health care claims database for 39 million commercially insured US populations. Patients with a TSC claim between 2000 and 2009, and continuous enrollment 12 months before and 12 months after their first TSC diagnosis were included in this analysis (These selection criteria lead to the exclusion of those at age less than one). Approximately 40 TSC related clinical conditions were identified using ICD-9 codes or CPT codes. The prevalence and incidence rates of these conditions are assessed and reported. RESULTS: Patients (N=1249) with TSC had mean age of 33.9 years at their 1st TSC diagnosis, and 57.5% were females. The most prevalent comorbid conditions within the first post TSC year were vision disorders (34.8%), benign neoplasm of skin (28.1%), seizure (16.1%), convulsion (15.0%), dyschromia (12.2%), depression (11.1%), cardiac dysrhythmia (9.1%), anxiety (8.6%), sleep disorder (7.8%) and hematuria (6.3%). The conditions with highest incidence rates (per 10,000 patient years) in the same period were benign neoplasm of skin (1,361), vision disorders (1,017), dyschrommia (480), seizure (464), and convulsion (456); subependymal giant cell astrocytoma (160) and Cardiac rhabdomyomas (80) were also observed. CONCLUSIONS: TSC affects multi-systems and organs, and is associated with many comorbid conditions. Vision disorders, benign skin cancer, seizure, convulsion, dyschromia, depression, cardiac dysrhythmia, anxiety, sleep disorders and hematuria are the most prevalent ones in the real world. Managing TSC could be challenging due to its multi-system involvement. Future effort should focus on developing treatment that treat the underlying cause of the disease.