Objective: To explore demographic-, health-, and smoking-related predictors and moderators of outcome in smokers who participated in two different brief smoking cessation interventions. Methods: Data were acquired using a quasi-randomized controlled trial that tested the efficacy of computer-generated tailored letters and physician-delivered brief advice against assessment only. Daily smokers (n = 1499) were recruited from 34 general medical practices. We used Generalized Estimating Equation analyses to investigate the relationship between 6-month prolonged smoking abstinence assessed at 12-, 18-, and 24-month follow-ups and potential predictors and moderators. Results: Female gender (OR = 1.49, 95% CI = 1.01-2.19), higher level of education (OR = 1.82, 95% CI = 1.18-2.82), intention to quit smoking (OR = 1.66, 95% CI = 1.16-2.38), and smoking cessation self-efficacy (OR = 1.30, 95% CI = 1.03-1.64) were positively, nicotine dependence (OR = 0.84, 95% CI = 0.76-0.94) and the presence of a smoking partner (OR = 0.60, 95% CI = 0.42-0.85) were negatively associated with smoking abstinence. Compared to assessment only, physician advice was less effective for people without an intention to quit smoking and for unemployed. Conclusion: Smoking cessation interventions might be improved by tailoring them to demographic- and smoking-related variables which were identified as predictors in this study. Practice implications: The results suggest that tailored letters are a more universally applicable brief intervention in general medical practice than physician advice. (C) 2009 Elsevier Ireland Ltd. All rights reserved.