OBJECTIVES: To profile real world treatment patterns of patients with tuberous sclerosis complex (TSC) which is a genetic disease that can affect multiple organ systems in the body. METHODS: We conducted a retrospective cohort study with a large national healthcare claims database that consists of 39 million commercially insured Americans between 2000 and 2009. Patients with a TSC claim and continuous enrollment 12 months before and 12 months after their first TSC diagnosis were included in the study (these selection criteria lead to the exclusion of those at age less than one). Resource utilization rates (measured as number of claims per patient) were examined for different provider types and places of services, and compared between the year before and after the first TSC diagnosis. Two-tail paired sample dependent t test and Chi-square test were used for pre-post comparisons as well as cross-region comparison. RESULTS: The included patients (N=1249) had a mean age of 33.9 years at their first TSC diagnosis, and 57.5% were female. Resource utilization rates with significant pre-post differences were inpatient admissions (0.16  vs. 0.08, p<0.01), emergency care (1.14 vs. 0.78, p<0.05), hospital outpatient care (12.68 vs. 6.66, p<0.05), neurologist care (0.60 vs. 0.32, p<0.05), neurological surgeon care (0.06 vs. 0.02, p<0.05), oncologist care (0.32 vs. 0.12, p<0.05), and the use of anti-epilepsy medications (2.45 vs. 2.10, p<0.05). The most common places of care were physician offices (21.44), hospital outpatient departments (12.68) and specialty care facilities (8.37); the most common provider specialties were primary care providers (6.07), neurologists (0.60), oncologists (0.32), surgeons (0.29); and the most common class of medications were anti-epilepsy medications (2.45). Significant cross-region variations in TSC medication utilization and costs were also observed (p<0.05). CONCLUSIONS: TSC patients had a very diverse treatment profile due to its multi-organ involvement. Future research is needed to explore the driving forces behind cross-region variations in TSC treatment.