Purpose: This paired-tooth randomized controlled prospective clinical study compared the clinical performance of three composite resins in Class III cavities after 12 months. Materials and Methods: Three materials were evaluated: a microfilled composite resin (Durafill VS), a hybrid composite resin (Filtek Z250), and a nanofilled composite resin (Filtek Supreme). Thirty-eight patients having at least three Class III restorations were enrolled in this study. A total of 114 restorations were placed by two calibrated operators according to the manufacturers' instructions. The adhesive system (Clearfil SE Bond) was either applied according to manufacturer's instructions (CSE non-etch) or enamel margins were first etched with phosphoric acid (CSE etch). One week later, the restorations were finished and polished. Two other independent examiners evaluated the restorations at baseline according to the USPHS criteria and USPHS modified criteria for the items color match and surface appearance. The restoration location was taken into consideration during the analysis of each item. A nonparametric analysis of variance (Friedman test) and the Wilcoxon test were used for statistical analysis (α = 0.05). Results: The restoration location did not influence the evaluated items. Filtek Z250 showed the best color match at baseline, and after 6 and 12 months. No significant difference in the item surface appearance was detected at baseline; however, after 6 and 12 months, Filtek Z250 showed the worst performance on this item. No significant difference was found between CSE non-etch and CSE etch groups. Conclusion: The hybrid composite resin showed an excellent immediate and 12-month color match, which was superior to the nanofilled and microfilled composites tested. On the other hand, the nanofilled and microfilled composites showed the best surface appearance after 12 months. Additional etching of the enamel cavity margins did not influence the clinical performance of the adhesive Clearfil SE Bond. Keywords: composite resin, baseline evaluation, class III cavities, nanofilled composite resin, microfilled composite resin, hybrid composite resin, self-etching adhesive.