Abstract Background The efficacy of the smoking-cessation agent varenicline has been reported in Asian smokers; however, few studies have investigated factors that contribute to lapse and relapse. Objective This post hoc analysis aimed to identify predictors of smoking lapse and relapse. Methods This was a post-hoc analysis based on a double-blind, placebo-controlled, randomized, parallel-group study in which Japanese smokers (aged 20–75 years) who smoked ≥10 cigarettes/day and were motivated to quit were randomized to receive varenicline (0.25 mg twice daily BID, 0.5 mg BID, 1 mg BID) or placebo for 12 weeks followed by a 40-week non-treatment follow-up. For inclusion in this analysis, participants must have been nicotine dependent (Tobacco Dependence Screener score ≥5) and must have successfully quit smoking continuously for 4 weeks (weeks 9–12). Lapse was defined by answering yes to ≥1 question in the Nicotine Use Inventory. Relapse was defined by participants having smoked for ≥7 days during follow-up measured by the Nicotine Use Inventory. Results Of the 619 randomized individuals, 515 had a Tobacco Dependence Screener score of ≥5, and 277 quit smoking continuously from weeks 9 to 12. Approximately 75% were male, with a mean (SD) BMI of 23.0 (3.0) kg/m2 . Maximum length of continuous abstinence (CA) during treatment and age (both P < 0.0001) were significant predictors of lapse. Maximum CA ( P < 0.0001), age ( P = 0.0002), Minnesota Nicotine Withdrawal Scale (MNWS) score for urge to smoke ( P = 0.0019), and having made ≥1 serious quit attempt ( P = 0.0063) were significant predictors of relapse. For participants with a maximum CA of 4 to 6 weeks versus those with a maximum CA of 10 to 11 weeks, the ORs for lapse and relapse were 4.649 (95% CI, 2.071–10.434) and 3.337 (95% CI, 1.538–7.239), respectively. In participants aged 21–34 years versus those aged 47–72 years, the ORs for lapse and relapse were 3.453 (95% CI 1.851, 6.441) and 3.442 (95% CI 1.795, 6.597), respectively. Participants with a MNWS urge to smoke score of 2 to 4 versus 0 had an OR for relapse of 3.175 (95% CI, 1.166–8.644). Participants having made ≥1 versus no serious quit attempts had an OR for relapse of 2.108 (95% CI, 1.168–3.805). Conclusion Shorter maximum CA and younger age at quit attempt were associated with increased risk of lapse and relapse. Higher MNWS urge to smoke score and having made ≥1 serious quit attempt were associated with increased relapse risk. ClinicalTrials.gov identifier: NCT00139750.