Background and aims: The majority of smokers accessing the current best treatments continue to smoke. We aimed to test if e-cigarettes (EC) compared with nicotine replacement treatment (NRT) can help such smokers to reduce smoking.

Design: Randomized controlled trial of EC (n = 68) versus NRT (n = 67) with 6-month follow-up.

Setting: Stop smoking service in London, UK.

Participants: A total of 135 smokers (median age = 40 years, 51% male) previously unable to stop smoking with conventional treatments.

Interventions: Participants received either NRT of their choice (8-week supply) or an EC starter pack and instructions to purchase further e-liquids of strength and flavours of their choice themselves. Products were accompanied by minimal behavioural support.

Measurements: Participants who reported that they stopped smoking or reduced their daily cigarette consumption by at least 50% at 6-month follow-up were invited to provide a carbon monoxide (CO) reading. The primary outcome was biochemically validated reduction in smoke intake of at least 50% at 6 months and the main secondary outcome was sustained validated abstinence at 6 months. Drop-outs were included as 'non-reducers'.

Findings: Validated smoking reduction (including cessation) was achieved by 26.5 versus 6.0% of participants in the EC and NRT study arms, respectively [relative risk (RR) = 4.4, P = 0.005, 95% confidence interval (CI) = 1.6-12.4]. Sustained validated abstinence rates at 6 months were 19.1 versus 3.0% (RR = 6.4, P = 0.01, 95% CI = 1.5-27.3). Product use was high and equal in both study arms initially, but at 6 months allocated product use was 47% in the EC arm versus 10% in the NRT arm (χ²₍₁₎ = 22.0, P < 0.001), respectively. Adverse events were minor and infrequent.

Conclusions: In smokers unable to quit using conventional methods, e-cigarettes were more effective than nicotine replacement therapy in facilitating validated long-term smoking reduction and smoking cessation when limited other support was provided.