Women are less successful than men at quitting smoking. We examined whether the male vs. female cessation outcome was influenced by baseline smoking behavior in participants who attempted to quit by using nicotine inhaler (NI) plus nicotine patch (NP) combination therapy. This double-blind, randomized, placebo-controlled trial enrolled 196 men and 204 women. Group 1 (99 men, 101 women) received NI plus NP (15 mg nicotine/16 h) for 6 weeks, then NI plus placebo patch (PP) for 6 weeks, then NI alone for 14 weeks. Group 2 (97 men, 103 women) received NI plus PP for 12 weeks, then NI alone for 14 weeks. Outcome measures were continuous self-reported abstinence and expired carbon monoxide concentration < 10 ppm. Baseline nicotine dependence was assessed by the Fagerström Test for Nicotine Dependence (FTND), and behavioral dependence by the 18-question Glover-Nilsson Smoking Behavioral Questionnaire (GN-SBQ). Male vs. female complete abstinence rates, regardless of treatment group, were 61.7% vs. 46.6% at 6 weeks (p = .0022), 42.3% vs. 30.9% at 12 weeks (p = .017), 30.1% vs. 17.6% at 6 months (p = .003), and 23.0% vs. 10.8% at 12 months, respectively (p = .001). Men had significantly higher baseline FTND (p = .0180) and lower total GN-SBQ (p < .0001) scores than women. In conclusion, women appear to have higher behavioral, and lower nicotine, dependence than men according to the GN-SBQ and the FTND; thus both nicotine and behavioral treatment should be tailored to women to increase their chances of abstinence.