Summary Background Tuberous sclerosis complex (TSC) is caused by mutations in TSC1 and TSC2, leading to mammalian target of rapamycin hyperactivation. Patients with TSC develop hamartomas in brain, lungs, liver and skin. Two epidemiological studies, performed in Minnesota, U.S.A., have estimated the incidence of TSC to be 0·28–0·56 per 100 000 person‐years (PY), based on < 12 patients. Furthermore, whether common comorbidities are associated with this rare disease is not known. Objectives To estimate the incidence of TSC and investigate the associations of TSC with other comorbidities, including diabetes, peptic ulcers, stroke and myocardial infarction. Methods We estimated the incidence and prevalence of TSC and its comorbidities from 1997 to 2010, based on the Catastrophic Illness Certificate disease database and a beneficiary cohort of 1 million people. Results The incidence of TSC in Taiwan is 0·153 per 100 000 PY. The number of patients identified with TSC in Taiwan doubled from 206 in 2006 to 471 in 2010. In 2010, the prevalence of TSC in Taiwan was estimated to be 1·58 in 100 000. We confirmed that female patients with TSC are more likely to develop renal tumours than male patients. Surprisingly, patients with TSC have a significantly decreased risk of developing peptic ulcers compared with controls. Conclusions This is the first large‐scale and longitudinal incidence study of TSC. This study provides compelling evidence that TSC mutations in humans are associated with a decreased risk of peptic ulcers. What's already known about this topic? Patients with tuberous sclerosis complex (TSC) develop systemic hamartomas with significant psychosocial burdens. Two small epidemiological studies have estimated the incidence of TSC to be 0·28–0·56 per 100 000 person‐years (PY) in the U.S.A. What does this study add? This 14‐year‐long longitudinal study estimated the incidence of TSC in Taiwan to be 0·153 per 100 000 PY. The prevalence of TSC in 2010 in Taiwan was 1·58 in 100 000. A significantly lower risk of peptic ulcer is found in patients with TSC compared with healthy controls. Linked Comment: Morrison and Donnelly. Br J Dermatol 2016; 174: 1184–1185.