The objective was to evaluate the clinical performance of a therapeutic sealant to arrest the progression of noncavitated approximal posterior carious lesions. The study population comprised 50 adolescents in whom bitewing radiographs had been taken for diagnosis of caries. Approximal noncavitated lesions in premolars and molars (4d–7m) were selected. One group (n=17) had a sealant placed after tooth separation on all enamel lesions. A second group (n=7) received sealant and fluoride varnish in a split-mouth design. A control group (n=26) received a standard fluoride varnish treatment without tooth separation. Follow-up radiographs were taken after 2 years and were analyzed together with the baseline radiographs in a blind study setting. About 93% of the sealed initial carious lesions showed no progression. The corresponding value for the fluoride varnish control group was 88%. In the split-mouth study, 92 and 88% of the surfaces with enamel caries showed no progression after sealant or fluoride varnish treatment, respectively. The difference between the two treatment procedures was not statistically significant. The incidence rate for the transition from enamel caries to dentin caries or fillings was 3.5–3.9 surfaces/100 years in the sealant groups and 5.9–6.1 surfaces/100 years in the fluoride varnish groups. The results show the potential of sealants to act as a noninvasive treatment of early approximal enamel lesions.