This randomized, prospective, and split-mouth study aimed to evaluate flowable bulk-fill resin composites in class II restorations, comparing it with a conventional layering technique after 4-year follow-up. Fifty-three subjects received three class II restorations according to the restorative systems: conventional microhybrid composite resin (PA - Peak Universal + Amelogen Plus, Ultradent); flowable bulk-fill and nanoparticulate composite resins (ABF - Adper Single Bond 2 + Filtek Bulk Fill Flow + Filtek Z350XT, 3M/Espe); and flowable bulk-fill and microhybrid composite resins, (XST - XP Bond + SDR + TPH3, Dentsply). The clinical performance and interproximal contacts were evaluated. Statistical analyses were performed using the Kaplan-Meier, equality test of two proportions, Friedman, Wilcoxon, Kruskal-Wallis, Mann-Whitney, and Logistic regression analysis tests (alpha = 0.05). In total, 106 restorations were evaluated at 4 years. Both systems with bulk-fill composites presented higher marginal discoloration than PA. About surface texture, ABF restorative system showed superior bravo scores being statistically similar to XST. Better performance for wear and surface staining was found for XST restorative system. All restorative systems resulted in the decreased interproximal contacts, occurring early for XST. The restorative systems that used flowable bulk-fill resin composites showed satisfactory clinical performance compared with conventional resin composite after 4 years. All restorative systems had decreased proximal contact after 4 years. Initial marginal discoloration was observed in more than 50% of class II restorations performed with restorative systems that used flowable bulk-fill resin composite. All restorative systems had decreased proximal contact strength over time.