Lung cancer screening programs provide an opportunity to support people who smoke to quit, but the most appropriate model for delivery remains to be determined. Immediate face-to-face smoking cessation support for people undergoing screening can increase quit rates, but it is not known whether remote delivery of immediate smoking cessation counselling and pharmacotherapy in this context also is effective. Does an immediate telephone smoking cessation intervention increase quit rates compared with usual care among a population enrolled in a targeted lung health check (TLHC)? In a single-masked randomized controlled trial, people 55 to 75 years of age who smoke and attended a TLHC were allocated by day of attendance to receive either immediate telephone smoking cessation intervention (TSI) support (starting immediately and lasting for 6weeks) with appropriate pharmacotherapy or usual care (UC; very brief advice to quit and signposting to smoking cessation services). The primary outcome was self-reported 7-day point prevalence smoking abstinence at 3months. Differences between groups were assessed using logistic regression. Three hundred fifteen people taking part in the screening program who reported current smoking with a mean ± SD age of 63 ± 5.4 years, 48%of whom were women, were randomized to TSI (n= 152) or UC (n= 163). The two groups were well matched at baseline. Self-reported quit rates were higher in the intervention arm, 21.1%vs8.9%(OR, 2.83; 95%CI, 1.44-5.61; P= .002). Controlling for participant demographics, neither baseline smoking characteristics nor the discovery of abnormalities on low-dose CT imaging modified the effect of the intervention. Immediate provision of an intensive telephone-based smoking cessation intervention including pharmacotherapy, delivered within a targeted lung screening context, is associated with increased smoking abstinence at 3months. ISRCTN registry; No.: ISRCTN12455871; URL: www.IRSCN.com.