Inattention and hyperactive-impulsive symptoms have been associated with nicotine dependence. In an open-label randomized trial (N = 454) of transdermal nicotine versus nicotine nasal spray, we examined whether increases in inattention and hyperactive-impulsive symptoms measured by self-report in the first quit week predicted relapse at the end of 8 weeks of treatment (EOT). During the first quit week, 166 (37%) participants reported an increase whereas 288 (63%) reported no change/decrease in total symptoms; changes were not influenced by treatment type. In a logistic regression model of abstinence, an increase in total symptoms in the first quit week significantly reduced odds of abstinence at EOT (continuous change score: OR = 0.94, 95% CI = 0.91-0.98, p = .002; dichotomized change score: OR = 0.57, 95% CI = 0.37-0.87, p = .009). Early increases in inattention and hyperactive-impulsive symptoms following quit date during nicotine replacement therapy predicted relapse to smoking, suggesting that treatments targeting these symptoms in the first quit week may facilitate abstinence.