Background: Prevalence of smoking among individuals with posttraumatic stress disorder (PTSD) is disproportionately high, and PTSD is associated with especially poor response to smoking cessation treatment. Objective: The current study examined whether integrating treatments for smoking cessation (varenicline plus smoking cessation counseling; VARCC) and PTSD (prolonged exposure therapy; PE) enhances smoking outcomes among smokers diagnosed with PTSD. Method: 142 adults with nicotine dependence (ND) and PTSD were randomized to a treatment program consisting of varenicline, smoking cessation counseling, and PE (VARCC + PE) or to VARCC only. Seven-day point prevalence abstinence (PPA) at posttreatment (3-months postquit day) and follow-up (6-months postquit day), verified by serum cotinine levels and exhaled carbon monoxide, was the primary smoking outcome. Psychological outcomes were PTSD and depression severity. Mixed effects models included baseline PTSD severity as a moderator of treatment condition effects. Results: Overall, VARCC + PE participants did not show greater PPA than VARCC participants. However, treatment effects were moderated by baseline PTSD severity. For participants with moderate and high PTSD severity, VARCC + PE led to significantly higher PPA than VARCC alone (ps<.05). No differences between treatment conditions emerged for participants with low baseline PTSD severity. Participants who received PE showed significantly greater reduction of PTSD and depression symptoms than those who did not receive PE. Conclusions: Integrating psychological treatment for PTSD and smoking cessation treatment enhances smoking cessation for participants with moderate or severe PTSD symptom severity, but does not enhance smoking cessation for participants with low baseline PTSD severity.