Abstract Introduction Many cancer patients who smoke report concurrent e-cigarette use. Using a mixed-methods approach, we aimed to (1) describe longitudinal e-cigarette use over 6 months after a cancer diagnosis and (2) assess the association between e-cigarette use and smoking cessation, among cancer patients in a smoking cessation trial. Aims and Methods Data were from a 2-site randomized controlled trial of Standard (brief counseling) versus Intensive treatment (sustained counseling plus smoking cessation medication) in individuals who smoke recently diagnosed with cancer. Participants (n = 303) reported e-cigarette use at baseline, 3 months, and 6 months. Biochemically-verified past 7-day cigarette abstinence was collected at 6 months. Qualitative interviews at 6 months explored factors related to e-cigarette use. Results E-cigarette use prevalence was highest between baseline and 3 months (16%) and declined over time. Participants using e-cigarettes at follow-up had higher baseline cigarette dependence and smoked more heavily. Multivariable analyses found no significant association between follow-up e-cigarette use and 6-month cigarette abstinence. E-cigarette use at follow-up was higher in the Standard versus Intensive treatment group (p = .003 and .001 at 3 and 6 mo, respectively). Smoking cessation and health concerns were primary reasons for using e-cigarettes. Conclusions Among individuals who smoke recently diagnosed with cancer and enrolled in a smoking cessation intervention trial, e-cigarette use during trial participation was not associated with smoking abstinence. Individuals who chose to use e-cigarettes were less likely to be receiving intensive cessation support as part of the trial. Further studies are needed to evaluate the association between e-cigarette use and smoking cessation in cancer patients. Implications E-cigarette use was not associated with cigarette abstinence at 6 months among adults who smoke recently diagnosed with cancer enrolled in a smoking cessation trial. Individuals with easier access to evidence-based smoking cessation treatment may be less likely to use e-cigarettes.