Epidemiologic studies of Creutzfeldt-Jakob disease (CJD) have been undertaken worldwide since the new variant CJD outbreak in 1996 in the United Kingdom. A nationwide report system, the Creutzfeldt-Jakob Disease Surveillance Unit (CJDSU), directed by the Centers for Disease Control of Taiwan, was established in 1997 to identify human prion diseases.From 1998 to 2017, 647 cases were referred to the committee for confirmation. The report to CJDSU included a structured questionnaire recording the clinical, demographic data, and potential iatrogenic exposure, and the results of the clinical and laboratory examination, including tests of blood and cerebrospinal fluid, electroencephalography, and brain magnetic resonance imaging.In total, 356 cases (women, n=178) were ascertained to be human prion diseases, and 97.4% (n=347) were sporadic CJD, including three definite, 314 probable, and 30 possible cases; one probable variant CJD and 8 cases of the genetic form human prion diseases. The age- and gender-specific average annual incidence were also significantly higher in the second decade (0.95/1,000,000) than in the first decade (0.63/1,000,000), with an incidence rate ratio of 1.51. The incidences increased with increasing age, reaching a peak at the age of 70-79 years. The 10-year survival curve for sCJD patients showed that the 1-, 5-, and 10-year cumulative survival rate were 52%, 5%, and 1%, respectively. PRNP polymorphisms in 170 patients showed that 98.8% were M129M and 97.6% E219E.The significant increase in incidence after 2008 suggests the increase in the awareness of this rare disease among physicians. The longer disease duration in patients with sCJD in Taiwan than in other countries indicates that the comprehensive support of the health care system, as well as the end-of-life care culture in Taiwan, may prolong survival time in patients with such a progressive and fatal disease.