OBJECTIVES:  : Despite lack of robust evidence on the adverse neuropsychiatric effects of bupropion and varenicline, the two commonly prescribed smoking cession agents, in 2009, the Food and Drug Administration (FDA) required a black box warning (BBW) on these medications. We investigated if there was a decline in use of bupropion and varenicline after the BBW by comparing the percent using these medications before and after BBW. METHODS:  We conducted a retrospective observational study using data from the Medical Expenditure Panel Survey from 2007 to 2011. The study sample consisted of adult smokers who were advised by their physicians to quit smoking (N=1,663 in 2007; N = 1,819 in 2008; N = 2,008 in 2009; N=1,776 in 2010 and N=1,962 in 2011). We used chi-square statistics, multivariable logistic, and segmented regressions to evaluate the change in use of these medications before and after the BBW. RESULTS:  Among users of varenicline, we observed a statistically significant decline from 10.6% in year 2007 to 2.3% in 2011 (p value<0.05). In the multivariable logistic (Adjusted Odds Ratio=0.35, 95% CI= 0.22-0.57) and segmented regressions (Odds Ratio =0.51, 95% CI=0.31-0.82) smokers who were advised to quit smoking by their physicians were less likely to use varencline in the post-BBW period as compared to the pre-BBW period. We did not observe significant differences in bupropion use between the pre- and post-BBW periods. CONCLUSIONS: The passage of FDA BBW was associated with a significant decline in the use of varenicline, but not in the use of bupropion. We speculate that bupropion use did not decline because it is also used to treat depression. There is a need for rigorous scientific studies on the causal link between bupropion and varenicline use and adverse neuropsychiatric symptoms.