The objective of this longitudinal clinical randomized trial was to evaluate the clinical performance of a nanofilled and a nanohybrid resin composite in Class I occlusal restorations of posterior teeth over the course of 54 months. Forty-one adolescents participated in the study. The teeth were restored with Adper Single Bond 2 (3M ESPE) and nanofilled (Filtek Z350, 3M ESPE), nanohybrid (Esthet-X, Dentsply) and microhybrid Filtek Z250 (3M ESPE) used as a control. After 54 months, the restorations were evaluated in accordance with the modified United States Public Health Service criteria. The McNemar and Friedman tests were used for statistical analysis, at a level of significance of 5%. Five failed restorations were observed during the follow-up. A change to unacceptable restoration occurred for one Esthet-X, two Filtek Z350, and two Filtek Z250 restorations, which received the clinically unacceptable score, Charlie, for both anatomic form and marginal adaptation. Secondary caries and postoperative sensitivity occurred in one Filtek Z250 and one Filtek Z350 restoration. When the five evaluation periods (baseline and six, 12, 30, and 54 months) were compared, significant differences were found in the marginal adaptation of Filtek Z250 and Filtek Z350. Significant differences in the roughness criteria (p=0.005) were also observed when the three composites were compared after 54 months (Filtek Z350 > Filtek Z250 > Esthet-X), always within clinically acceptable limits. The materials investigated showed acceptable clinical performance for Class I restoration after 54 months. Long-term reevaluations are necessary for a more detailed analysis of these composites.