Cotinine, a metabolite of nicotine, has been used to study tobacco smoke exposure in population studies, but the authors are unaware of its use to screen hospitalized patients. The authors measured serum cotinine levels in 948 patients admitted to an urban public hospital in San Francisco, California, between September 2005 and July 2006. On the basis of cotinine levels, they classified patients as active smokers (cotinine > or = 14 ng/mL), recent smokers or significantly exposed to secondhand smoke (SHS) (0.5-13.9 ng/mL), lightly exposed to SHS (0.05-0.49 ng/mL), or unexposed (<0.05 ng/mL). In contrast to the 13% prevalence of smoking in the general population of San Francisco, 40% of patients were active smokers; 15% were recent smokers or heavily exposed to SHS; 25% had low-level exposure to SHS; and 20% were unexposed. Active smoking or heavy SHS exposure was particularly high among African Americans (77%), the uninsured (65%), self-reported alcohol drinkers (77%), and illicit drug users (90%). Of people who denied smoking, 32% were found to have had significant exposure. If serum cotinine measurement became part of routine screening at urban public hospitals, cotinine levels would be abnormal in many patients and would provide objective evidence of tobacco smoke exposure, probably resulting in more intensive intervention to encourage patients to stop smoking and avoid SHS.