Sealants are an effective method of prevention and treatment for early caries lesions. This study analyzed the 1-year clinical performance of resin-based and ionomeric sealants applied to permanent teeth under different humidity conditions. The investigation was a triple-blind randomized clinical trial (RCT) with a four arms split-mouth design, divided according to the sealant protocol: (1) Resin-based sealant applied with rubber dam isolation, (2) Resin-based sealant applied with cotton rolls isolation, (3) Ionomeric sealant applied with rubber dam isolation and (4) Ionomeric sealant applied with cotton rolls isolation. Fifty-eight patients started the study (232 teeth), and 47 (188 teeth) remained until the 1-year recall. The modified USPHS criteria were used in the analyzes to investigate surface texture, retention and the presence of secondary caries lesions around the sealants; in the following periods: baseline, after 3, 6, 9, and 12months by two calibrated examiners. Data were analyzed by the Mann-Whitney and Friedman tests. There was no difference between the types of sealants (p > 0.05). The type of humidity control influenced the superficial texture (p = 0.0012) and the retention of sealants (p = 0.0023). The sealant displacement was greater under cotton rolls isolation. Only one active caries lesion in enamel was found in the 9th month. It may be concluded that sealants effectively prevented caries, even when they were partially or totally lost, regardless of the material. The rubber dam isolation with a rubber dam promoted lower surface roughness and improved the retention rates. International Clinical Trials Registry Platform: #1111-1215-2832 (07/26/2018).