Background and Aims: Previous epidemiological data on the association between cigarette smoking and risk of gallstone development remain controversial, and most relevant studies have relied on self-reported questionnaires. We aimed to elucidate this association using both an objective biomarker of tobacco exposure (urinary cotinine) and a self-reported questionnaire.

Methods: We analyzed 221,721 asymptomatic adults who underwent abdominal ultrasonography and urinary cotinine measurement between January 2011 and December 2016. Cotinine-verified current smokers were defined as participants with urinary cotinine levels ≥50 ng/mL.

Results: The mean age of the study population was 35.9 years, and the proportion of men was 55.8%. The proportions of self-reported and cotinine-verified current smokers were 21.3% and 21.2%, respectively. After adjusting for confounding factors, self-reported current smoking was associated with an increased risk of gallstone development [adjusted odds ratio (aOR) 1.14; 95% confidence interval (95%CI), 1.04–1.25]. Moreover, among the current smokers, the risk of gallstone development increased with an increase in the amount of cigarette smoking (<20 and ≥20 pack-years vs. never smoked; aOR=1.11 and 1.25; 95%CI: 1.01–1.22 and 1.07–1.45, respectively). Cotinine-verified current smoking was also associated with an increased risk of gallstone development (aOR=1.16; 95%CI: 1.07–1.25). Among the self-reported never or former smokers, the cotinine-verified current smokers (aOR=1.20; 95%CI: 1.01–1.44) showed a significantly higher risk of gallstones than cotinine-verified never smokers.

Conclusions: Cotinine-verified and self-reported current smoking were independent risk factors for gallstones, suggesting a distinct role of tobacco smoking in gallstone development.


smoking, cotinine, gallstone