Aims. Although nicotine replacement therapy (NRT) has been used to aid smoking cessation for the last 20 years, little information exists on the effect of nicotine products on the oral mucosa, particularly with regard to the direct effect at the site of application. This study aimed to assess the oral safety of a new sublingual tablet containing 2 mg nicotine with regard to lesions at the site of application. Design. Prospective follow-up to 12 months of smokers using the 2-mg sublingual tablet over a period of 3-6 months. Setting. A smoking cessation programme Participants. Thirty smokers. Measurements. Oral mucosa was inspected and photographed at each visit. At 6 months, subjects were asked for consent to take a biopsy from the site of application. Findings. Spontaneous smoking cessation outcome at 12 months was 27% allowing for lapses. At baseline 21 mucosal lesions were diagnosed in 15 subjects. After 6 months eight lesions were observed in six subjects. The predominant diagnosis at all visits was melanin pigmentation. Eight subjects had lesions in the floor of the mouth during the 6-month medication period, all of which appeared in the first 1-6 weeks of treatment. By the 6-month visit all such lesions had resolved. The local symptoms were all mild and tolerable. Conclusion. The sublingual tablet appears to be a safe form of administration of nicotine with mild and transient effects on the floor of the mouth.