This study aimed to evaluate the efficacy of non-invasive and micro-invasive treatments on the arrest of occlusal enamel carious lesions in erupting permanent molars. This two-arm randomized clinical trial included 27 subjects, aged 5-11 years, with 64 erupting permanent molars presenting active occlusal enamel carious lesions (as assessed by the International Caries Detection and Assessment System [ICDAS]; scores 1-3). The sample was randomly assigned into two treatment groups: 1) resin-modified glass ionomer cement sealant (Clinpro XT Varnish; 3M ESPE) and 2) 4-week topical fluoride varnish application (Duraphat; Colgate). All children and parents received oral hygiene and dietary instructions. Teeth were evaluated at baseline and 3, 6, 9, and 12 months regarding the eruption stage, biofilm accumulation, as well as severity and activity of the carious lesions. The Kaplan-Meier method was used to evaluate the survival estimates for inactivation of the carious lesions for both treatment groups. Multivariate Cox regression models with shared frailty were performed to identify factors associated with the outcome (p < 0.05). After 12 months, 22% and 3% of the lesions treated with topical fluoride varnish and sealant, respectively remained active. The adjusted model demonstrated that younger children had a higher probability of active enamel carious lesions arresting (hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.22-0.78; p=0.01). However, the probability of active enamel carious lesions arresting after sealant application was 8.85 times higher compared with fluoride varnish applications (p=0.01). Sealing is a more effective approach than fluoride varnish for arresting occlusal enamel carious lesions in erupting permanent molars.