Objective: To determine whether over-the-counter (OTC) nicotine replacement therapy (NRT) is pharmacologically efficacious, whether it produces abstinence rates similar to those in prescription settings, and to estimate the long term (that is, greater than six month) abstinence rate with OTC NRT. Method: Systematic literature review. Data sources: Medline, Psych Abstracts, bibliographies, requests of scientists. Study selection: Studies comparing OTC NRT versus OTC placebo or studies comparing OTC NRT versus prescription NRT that reported abstinence rates and for which a full study report was available. Data extraction: Two of the authors independently reviewed studies and compared results. Data synthesis: Meta-analysis was performed by first testing for homogeneity across studies, then combining odds ratios (ORs) weighting by inverse variance and proportions weighting by study sample size. Results: One OTC NRT versus OTC placebo nicotine gum study was excluded due to small sample size and different setting. The four remaining studies were randomised trials of nicotine versus placebo patch with ORs of 2.1–3.2. These outcomes were homogenous and when combined resulted in an OR favouring NRT of 2.5 (95% confidence interval (CI) 1.8 to 3.6). Among the two randomised and two non-randomised trials of OTC NRT versus prescription NRT, one small study had an OR of 0.3, two others had ORs of 1.0 and 1.4, and a fourth study had an OR of 3.6. These results were not homogenous; however, when combined via a random effects model the estimated OR was not less than 1.0—that is, OR 1.4 (95% CI 0.6 to 3.3). The long term (that is, greater than six months) quit rates for OTC NRT was 1% and 6% in two studies and 8–11% in five other studies. These results were not homogenous; however, when combined the estimated OR was 7% (95% CI 4% to 11%). Conclusions: OTC NRT is pharmacologically efficacious and produces modest quit rates similar to that seen in real world prescription practice.