Background:Despite strong efficacy in randomized trials, the population effectiveness of pharmaceutical aids in long-term smoking cessation is lacking, possibly because of confounding (factors that are associated with both pharmaceutical aid use and difficulty quitting). Matching techniques in longitudinal studies can remove this confounding bias. Methods:Using the nationally representative Tobacco Use Supplement to the Current Population Survey (TUS-CPS), we assessed the effectiveness of medications to aid quitting among baseline adult smokers who attempted to quit prior to one year of follow-up in two longitudinal studies: 2002-2003 and 2010-2011. Pharmaceutical aid users and nonusers with complete data (n = 2129) were matched using propensity score models with 12 potential confounders (age, sex, race-ethnicity, education, smoking intensity, nicotine dependence, previous quit history, self-efficacy to quit, smoke-free homes, survey year, and cessation aid use). Using matched data sets, logistic regression models were fit to assess whether use of any individual pharmaceutical aid increased the proportion of patients who were abstinent for 30 days or more at follow-up. Results:Propensity score matching markedly improved balance on the potential confounders between the pharmaceutical aid use groups. Using matched samples to provide a balanced comparison, there was no evidence that use of varenicline (adjusted risk difference [aRD] = 0.01, 95% confidence interval [CI] = -0.07 to 0.11), bupropion (aRD = 0.02, 95% CI = -0.04 to 0.09), or nicotine replacement (aRD = 0.01, 95% CI = -0.03 to 0.06) increased the probability of 30 days or more smoking abstinence at one-year follow-up. Conclusions:The lack of effectiveness of pharmaceutical aids in increasing long-term cessation in population samples is not an artifact caused by confounded analyses. A possible explanation is that counseling and support interventions provided in efficacy trials are rarely delivered in the general population.