BackgroundQuitting smoking is difficult and many people who smoke experience cessation fatigue (CF) as a result of multiple failed attempts. This study examined the association of CF with making and sustaining a smoking quit attempt. MethodsData analysed were 4,139 adults (aged 18 years or older) who smoked daily or weekly and participated in the 2018 and 2020 International Tobacco Control Four Country Smoking and Vaping Surveys (ITC 4CV) conducted in Australia, Canada, England, and the US. CF was assessed at baseline using a single question: “To what extent are you tired of trying to quit smoking?” with response options: “Not at all tired”; “Slightly tired”; “Moderately tired”; “Very tired”; or “Extremely tired”. We used binary logistic regression models to test the hypothesis that baseline CF would predict lower odds of both making a quit attempt and sustaining abstinence for a month or longer at follow-up adjusted for socio-demographic and smoking/vaping-related covariates. ResultsPersons who currently smoked and reported at least some CF were more likely to make a quit attempt, but less likely to sustain abstinence for at least one month, than those who reported no CF. These associations were independent of socio-demographic variables, and they did not differ by country. ConclusionContrary to expectation, CF was positively associated with making a quit attempt and non-linearly associated with lower rates of sustained abstinence at follow-up. While these findings should be replicated, they suggest that people with CF may benefit from targeted support to remain abstinent after a quit attempt.