BACKGROUND: Nicotine replacement therapy (NRT) has proven effect in assisting smoking cessation. However, its effectiveness varies across studies and population groups. This may be due to differences in the rate of adherence. Hence, this review aims to examine the level of adherence to NRT and to assess if the level of adherence to NRT affects success of smoking cessation. METHODS: A systematic review and meta-analysis was conducted using studies retrieved from five electronic databases (MEDLINE, Scopus, EMBASE, Web of science, and PsycINFO) and grey literature. Pooled analysis was conducted using Stata version 16 software. Methodological quality and risk of bias were assessed using the NIH Quality Assessment Tool. Analyses were done among those studies that used similar measurements to assess level of adherence and successful smoking cessation. Heterogeneity of studies was assessed using the Higgins' I2 statistical test. Funnel plots and Egger's regression asymmetry test were used to affirm presence of significant publication bias. RESULTS: A total of 7521 adult participants of 18 years old and above from 16 studies were included in the analysis. Level of adherence to NRT among participants of randomised controlled trials were found to be 61% (95% CI, 54-68%), p-value of < 0.001 and I2 = 85.5%. Whereas 26% of participants were adherent among participants of population-based studies with 95% CI, 20-32%, p-value of < 0.001 and I2 = 94.5%. Level of adherence was the lowest among pregnant women (22%) with 95% CI, 18-25%, p-value of 0.31 and I2 = 15.8%. Being adherent to NRT doubles the rate of successful quitting (OR = 2.17, 95% CI, 1.34-3.51), p-value of < 0.001 and I2 = 77.6%. CONCLUSIONS: This review highlights a low level of adherence to NRT among participants of population-based studies and pregnant women as compared to clinical trials. Moreover, the review illustrated a strong association between adherence and successful smoking cessation. Hence, it is recommended to implement and assess large scale interventions to improve adherence. Health programs and policies are recommended to integrate the issue of adherence to NRT as a core component of smoking cessation interventions. TRIAL REGISTRATION: PROSPERO registration number: CRD42020176749 . Registered on 28 April 2020.