Context Serum total bilirubin levels in healthy patients reflect genetic and environmental factors that could influence the risk of developing respiratory disease.Objective To examine the relationship between bilirubin levels and respiratory disease.Design, Setting, and Participants Cohort study among 504 206 adults from a UK primary care research database (the Health Improvement Network) with serum bilirubin levels recorded but no evidence of hepatobiliary or hemolytic disease. Data were recorded between January 1988 and December 2008.Main Outcome Measures Incidence of chronic obstructive pulmonary disease (COPD), lung cancer, and all-cause mortality.Results Median bilirubin levels were 0.64 mg/dL (interquartile range, 0.47-0.88 mg/dL) in men and 0.53 mg/dL (interquartile range, 0.41-0.70 mg/dL) in women. There were 1341 cases of lung cancer, 5863 cases of COPD, and 23 103 deaths, with incidence rates of 2.5, 11.9, and 42.5 per 10 000 person-years, respectively. The incidence of lung cancer per 10 000 person-years in men was 5.0 (95% confidence interval [CI], 4.2-6.0) in the first decile category of bilirubin compared with 3.0 (95% CI, 2.3-3.8) in the fifth decile. The corresponding incidences for COPD in men were 19.5 (95% CI, 17.7-21.4) and 14.4 (95% CI, 12.7-16.2). The mortality rates per 10 000 person-years in men were 51.3 (95% CI, 48.5-54.2) in the first decile category compared with 38.1 (95% CI, 35.5-40.8) in the fifth decile. The associations were similar for women. After adjusting for other important health indicators, regression estimates for incidence rate of lung cancer per 0.1-mg/dL increase in bilirubin level were an 8% decrease (95% CI, 5%-11%) for men and an 11% decrease (95% CI, 7%-14%) for women. The regression estimate for COPD in men per 0.1-mg/dL increase in bilirubin level was a 6% decrease (95% CI, 5%-7%) and for mortality in men was a 3% decrease (95% CI, 2%-3%) after accounting for other health indicators. The results for COPD and mortality in women were very similar.Conclusion Among patients with normal-range bilirubin levels in primary care practices, relatively higher levels of bilirubin were associated with a lower risk of respiratory disease and all-cause mortality. JAMA. 2011;305(7):691-697 www.jama.com