Objective: The treatment of non-small cell lung cancer depends on the stage, and this is clinically best determined by using fluorodeoxyglucose-positron emission tomography/computed tomography. We evaluated the effect smoking has on the accuracy of this test. Methods: We performed a prospective cohort study evaluating the accuracy of clinical stage compared with pathologic stage between cigarette smokers and nonsmokers with non-small cell lung cancer. All patients were assigned a clinical TNM stage after fluorodeoxyglucose-positron emission tomographic/computed tomographic scanning and then underwent meticulously pathologic TNM staging. If N2, N3, or M1 negative, patients underwent thoracotomy with complete thoracic lymphadenectomy. The clinical and pathologic stages were compared. Results: There were 246 patients: 52 never smoked (NS group), 112 quit at least 1 month before fluorodeoxyglucose-positron emission tomography/computed tomography (Q group), and 82 were still smokers (S group). The 3 groups were similar for stage and histology. The overall accuracy was 83%, 80%, and 64% for the NS, Q, and S groups, respectively (P = .03). The accuracy for the T status was 88%, 84%, and 86%; accuracy for the N2 lymph nodes was 96%, 75%, and 72%; and accuracy for the N1 lymph nodes was 92%, 78%, and 80%, respectively, favoring the NS group. The greater the pack-year history, the greater the N2 inaccuracy (P = .04). Multivariate analysis showed that status of smoking (P = .026) and maxSUV value (P = .014) were independent predictors of fluorodeoxyglucose-positron emission tomography/computed tomography accuracy. Conclusions: Patients with non-small cell lung cancer who continue to smoke at the time of their fluorodeoxyglucose-positron emission tomographic/computed tomographic scan have less accurate clinical staging compared with those who stopped 1 month before or who never smoked. As the pack-years increase, the accuracy for the N2 nodes decrease. Nonsmokers have the most accurate clinical staging. © 2006 The American Association for Thoracic Surgery.