Background: Nicotine Replacement Therapy (NRT) was licensed for harm reduction in the UK in 2005, and guidance to UK Stop Smoking Services (SSS) to include long-term partial or complete substitution of cigarettes with NRT was issued in 2013. Yet, NRT prevalence data and data on changes in biomarkers associated with long-term NRT use among SSS clients are scarce.Methods: SSS clients abstinent 4 weeks post-quit date were followed up at 12 months. At baseline standard socio-demographic, smoking and SSS use characteristics were collected and of those eligible, 60.6% (1,047/1,728) provided data on smoking status and NRT use at follow-up. A subsample also provided saliva samples at baseline and of those eligible, 36.2% (258/712) provided follow-up samples. Saliva was analysed for cotinine (a metabolite of nicotine) and alpha-amylase (a stress biomarker).Results: Among those who had used NRT during their initial quit attempt (61.5%, 95%CI 58.4-64.6), 6.0% (95%CI 4.3-8.3%) were still using NRT at one year, significantly more ex-smokers than relapsed smokers (9.5% vs. 3.7%; p=0.005). In adjusted analysis, NRT use interacted with smoking status to determine change in cotinine, but not alpha-amylase, levels (Wald χ2 (1)=13.0, p<0.001): cotinine levels remained unchanged in relapsed smokers and ex-smokers with long-term NRT use but decreased in ex-smokers without long-term NRT use.Conclusions: Long-term NRT use is uncommon in SSS clients, particularly among relapsed smokers. Its use is associated with continued high intake of nicotine among ex-smokers but does not increase nicotine intake in smokers. It does not appear to affect stress response.IMPLICATIONS Little is known about the long-term effects of Nicotine Replacement Therapy (NRT). Given an increasing shift towards harm reduction in tobacco control, reducing the harm from combustible products by complete or partial substitution with non-combustible products, more data on long-term use are needed. This study shows that in the context of stop smoking services, clients rarely use products for up to a year and that NRT use does not affect users’ stress response. Ex-smokers using NRT long-term can completely replace nicotine from cigarettes with nicotine from NRT; long-term NRT use by continuing smokers does not increase nicotine intake. Long-term NRT appears to be a safe and effective way to reduce exposure to combustible nicotine.