BACKGROUND: Continued smoking in cancer patients undergoing treatment results in significantly higher rates of treatment toxicities and persistent effects, increased risk of recurrence and second malignancy, and increased all-cause mortality. Despite this, routine tobacco use screening and the provision of smoking cessation treatment has yet to be implemented widely in the cancer setting. OBJECTIVE: The objective of this study was to implement and evaluate the adoption and impact of an innovative Smoking Cessation e-referral System (CEASE) to promote referrals to smoking cessation programs in cancer patients. METHODS: A patient-directed electronic smoking cessation platform (CEASE) was developed to promote smoking screening and referral and implemented at 1 of Canada's largest cancer centers. The implementation and evaluation were guided by the Ottawa Model of Research Use. An interrupted time series design was used to examine the impact of CEASE on screening rates, referrals offered, and referrals accepted compared with a previous paper-based screening program. A subsample of smokers or recent quitters was also assessed and compared pre- and postimplementation to examine the effect of CEASE on subsequent contact with smoking cessation programs and quit attempts. RESULTS: A total of 17,842 new patients attended clinics over the 20-month study period. The CEASE platform was successfully implemented across all disease sites. Screening rates increased from 44.28% (2366/5343) using the paper-based approach to 65.72% (3538/5383) using CEASE (P<.01), and referrals offered to smokers who indicated interest in quitting increased from 18.6% (58/311) to 98.8% (421/426; P<.01). Accepted referrals decreased from 41% (24/58) to 20.4% (86/421), though the overall proportion of referrals generated from total current/recent tobacco users willing to quit increased from 5.8% (24/414) to 20.2% (86/426) due to the increase in referrals offered. At 1-month postscreening, there was no significant difference in the proportion that was currently using tobacco and had not changed use in the past 4 weeks (pre: 28.9% [24/83] and post: 28.8% [83/288]). However, contact with the referral program increased from 0% to 78% in the postCEASE cohort (P<.001). CONCLUSIONS: CEASE is an innovative tool to improve smoking screening and can be implemented in both a time- and cost-effective manner which promotes sustainability. CEASE was successfully implemented across all clinics and resulted in improvements in overall screening and referral rates and engagement with referral services.