Considering xenogeneic collagen matrix (CM) and enamel matrix derivative (EMD) characteristics, it is suggested that their combination could promote superior clinical outcomes in root coverage procedures. Thus, the aim of this parallel, double-masked, dual-center, randomized clinical trial is to evaluate clinical outcomes after treatment of localized gingival recession (GR) by a coronally advanced flap (CAF) combined with CM and/or EMD. Methods: Sixty-eight patients presenting one Miller Class I or II GRs were randomly assigned to receive either CAF (n = 17); CAF + CM (n = 17); CAF + EMD (n = 17), or CAF + CM + EMD (n = 17). Recession height, probing depth, clinical attachment level, and keratinized tissue width and thickness were measured at baseline and 90 days and 6 months after surgery. Results: The obtained root coverage was 68.04% ± 24.11% for CAF; 87.20% ± 15.01% for CAF + CM; 88.77% ± 20.66% for CAF + EMD; and 91.59% ± 11.08% for CAF + CM + EMD after 6 months. Groups that received biomaterials showed greater values (P <0.05). Complete root coverage (CRC) for CAF + EMD was 70.59%, significantly superior to CAF alone (23.53%); CAF + CM (52.94%), and CAF + CM + EMD (51.47%) (P <0.05). Keratinized tissue thickness gain was significant only in CM-treated groups (P <0.05). Conclusions: The three approaches are superior to CAF alone for root coverage. EMD provides highest levels of CRC; however, the addition of CM increases gingival thickness. The combination approach does not seem justified Ver menos