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The objective of the study was to compare cause-specific mortality risks in the periods before and after the introduction of accurate and specific serological tests for diagnosing celiac disease.This was a prospective cohort study of people with celiac disease diagnosed in Southern Derbyshire, United Kingdom, from the late 1950s onward, and followed-up from 1978 until death or 31 December 2006. Standardized mortality ratios (SMRs) were calculated for all-cause mortality and various cause-specific groups concentrating on the period commencing 2 years after diagnosis of celiac disease.A total of 1,092 celiac patients (of whom 90% were incident) contributed 10,152 person-years of follow-up beyond 2 years of diagnosis and 142 deaths. A statistically significant increase in all-cause mortality was observed (SMR 1.37; 95% confidence interval (CI) 1.16–1.62), along with an increase in deaths from cancer (SMR 1.61; 95% CI 1.19–2.13), digestive disease (SMR 2.19; 10 deaths, 4 due to liver disease), and respiratory disease (SMR 1.57; 21 deaths, 11 due to pneumonia). The overall increase in mortality risk was higher for males (SMR 1.86; 95% CI 1.45–2.34) than it was for females (SMR 1.10; 95% CI 0.86–1.38). When results were stratified by period of diagnosis (pre-1990, 1990–1999, and 2000 onward), we found no evidence of differing all-cause mortality between cases diagnosed within these periods.Mortality in people with celiac disease has not materially changed over the 25 years of this study with the introduction of serological tests to aid diagnosis. The excess overall mortality we observed was partly explained by deaths from cancer, digestive disease, and respiratory diseases, of which the majority were deaths from pneumonia, supporting existing guidelines that advise pneumococcal vaccination for celiac patients.