PURPOSE: Markers of genetic susceptibility to tobacco-related cancers could personalize harms of smoking and motivate cessation. Our objective was to assess whether a multicomponent intervention that included feedback about genetic susceptibility to lung cancer increased risk perceptions and rates of smoking cessation compared with a standard cessation intervention. EXPERIMENTAL DESIGN: Our design was a two-arm trial with eligible smokers randomized in a 1:2 ratio to Enhanced Usual Care or Biomarker Feedback (BF). Surveys were conducted at baseline, 6, and 12 months later. The setting was an inner city community health clinic. African-American patients who were current smokers (n = 557) were identified by chart abstraction and provider referral. All smokers received a self-help manual and, if appropriate, nicotine patches. Smokers in the BF arm also were offered a blood test for genotyping the GST(3) gene (GSTM1), sent a test result booklet, and called up to four times by a health educator. Prevalent abstinence was assessed by self-report of having smoked no cigarettes in the prior 7 days at the 6- and 12-month follow-ups and sustained abstinence, i.e., not smoking at either follow-up or in-between. RESULTS: Smoking cessation was greater for the BF arm than the Enhanced Usual Care arm (19% versus 10%, respectively; P < 0.006) at 6 months but not at 12 months. CONCLUSIONS: Smokers agreed to genetic feedback as part of a multicomponent cessation program. Although the program increased short-term cessation rates compared with standard intervention, genetic feedback of susceptibility may not benefit smokers with high baseline risk perceptions.