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The aim of this study is to detect the main individual and transportation factors associated with obesity and its prevalence among Italian professional drivers (PDs).We performed a cross-sectional questionnaire survey. Data from PDs (n = 497) were used for analyses.Sixty-one percent of participants were either overweight or obese according to their body mass index. Predictive factors for obesity were traveling more than 40,000 miles per year (odds ratio [OR] 4.20, confidence interval [CI] 1.41–12.56) and hours spent behind the wheel per day (OR 1.27, CI 1.02–1.58). Bus drivers had half the risk of being obese compared to truck drivers (OR 0.45, CI 0.23–0.87). An inverse association was detected between educational attainment and obesity (OR 0.32, CI 0.11–0.90).PDs with high number of driving hours per day, miles driven per year, and low educational level should be subject to special educational programs to reduce and prevent obesity. Am. J. Ind. Med. 58:212–219, 2015. © 2015 Wiley Periodicals, Inc.