Around 85% of stop-smoking attempts using ‘gold-standard’ cessation treatment fail. New Zealand’s goal of lowering smoking rates to 5% by 2025 is thus unlikely to be achieved unless more effective treatments quickly become available. Even if the target is achieved, many of the remaining 250,000 smokers will have alcohol, drug, and/or mental health problems along with very high tobacco dependence. These people are even less likely to quit by using existing treatments that are typically ‘one-size-fits-all’ and do not adapt to their needs. We therefore plan to conduct a randomised trial to determine whether smokers with these problems, who do not appear to be benefiting from varenicline (the most effective cessation medication) early on in their quit attempt, are more likely to quit smoking for six months if we adapt their treatment by supplementing varenicline with other products (nicotine patch, bupropion, or nicotine-containing e-cigarettes), compared to remaining on varenicline alone.