Smoking cessation improves quality of life (QOL) in the general population. However, there is limited information on the role of smoking status on QOL among cancer patients. Moreover, previous studies tended to analyze smoking status dichotomously and at a single point in time, potentially reducing the strength of the relation between smoking cessation and QOL. This study examined the association of smoking abstinence and QOL over time, including depression, pain, and fatigue in patients with a wide variety of cancers. Participants were 332 cancer patients (eg, gynecologic, breast, thoracic, head and neck, and genitourinary) who had been abstinent for at least 24 hours. Days abstinent and QOL were assessed at baseline and 2, 6, and 12 months later. Latent growth curve models examined if days abstinent was associated with QOL at each assessment. Baseline demographics (eg, sex and income) and smoking history variables (eg, nicotine dependence) were used as time-invariant covariates. The final model for each QOL component had good-to-excellent fit. More days abstinent was associated with lower depression at all follow-ups and with lower fatigue at 12 months but was not associated with pain. QOL was better among patients who quit smoking for longer periods. Findings suggest different timelines, with smoking abstinence most immediately associated with lower depression, followed by lower fatigue. Although pain decreased over time, it was not associated with length of smoking abstinence. Results reinforce the relationship between sustained smoking cessation and QOL, which should be communicated to patients. © 2019 John Wiley & Sons, Ltd.