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Previous studies suggested increased morbidities and mortalities of liver diseases in drivers.To examine whether driving (monthly driving distance; tenure) is associated with elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), or chronic fatty liver (FL) changes, we performed a cross-sectional, secondary analysis of the Taxi Drivers' Health Study (n = 1,355), adjusting for clinical, demographic, and lifestyle factors.Prevalence of elevated ALT, elevated AST, and fatty liver changes were 22.0%, 5.1%, and 9.3%, respectively. Driving distance had a positive association with elevated ALT with a prevalence ratio of 1.35 (95% CI: 0.98, 1.89) comparing the highest versus lowest driving quartile. This association differed by alcohol use, with a corresponding prevalence ratio of 2.08 (95% CI: 1.30, 3.33) among “past/current” drinkers but no association among “never” drinkers. Similar patterns were found for AST, but estimates were less stable. We found a curvilinear response pattern for fatty liver changes; prevalence first increased with years as a taxi driver and then receded in the highest ranges of driving tenure, regardless of the alcohol history.Our results provide evidence that long driving is associated with both short-term and chronic liver insults, although alcohol use appears to modify this putative effect. Am. J. Ind. Med. 54:618-627, 2011. © 2011 Wiley-Liss, Inc.