Smoking remains the leading cause of preventable death globally, with high prevalence in disadvantaged populations despite access to free nicotine replacement therapy (NRT) and counseling through Ontario's STOP Program. This study aims to evaluate the acceptability, feasibility, and comparative effectiveness of e-cigarettes and cytisine as harm-reduction tools for individuals who continue to smoke despite standard treatments. Over four years, 6,000 STOP participants who smoke ≥5 cigarettes daily at six months post-treatment will be randomized to receive either an e-cigarette starter kit or a 28-day cytisine supply. Data will be collected via REDCap and include biomarkers (NNAL, PAH), self-reported smoking behavior, nicotine dependence, and quality of life. Statistical analyses will assess changes and compare outcomes between groups. Results will inform public health strategies and enhance equitable cessation support for underserved populations.

Inclusion Criteria:

1. Willingness to comply with all study procedures, for the full duration of the study period (12 months);
2. Age 18 years or older;
3. Currently smoking 5 or more cigarettes daily; and
4. Must have regular access to a phone and email to receive study communications and complete study monitoring.

Exclusion Criteria:

1. Individuals who smoke only occasionally or have quit smoking prior to the 6-month follow-up;
2. Daily or almost daily users of e-cigarettes for the past 30 days;
3. Presence of medical or psychiatric conditions that may interfere with safe participation or compliance with the study protocol, including severe cardiovascular disorders, renal impairment or respiratory conditions;
4. Known allergy or hypersensitivity to any components of the e-cigarettes, e-liquids, or cytisine;
5. Pregnant or breastfeeding, or planning to become pregnant within the next 12 months; or
6. Current use of pharmacological smoking cessation aids or participation in other smoking cessation clinical trials.