The aim of this study was to evaluate whether the use of enamel matrix derivative (EMD) improves clinical results of the coronally advanced flap (CAF) procedure in the treatment of multiple gingival recession defects. Ten patients presenting at least two adjacent buccal gingival recession defects affecting symmetric teeth on both sides of the maxilla were included in this study. Each set of multiple recession defects was assigned randomly to the test or control group. A bilateral simultaneous CAF procedure with vertical releasing incisions, with the adjunct of EMD for test sites, was performed. Clinical measurements (recession length, keratinized tissue, probing depth, and clinical attachment level) were assessed at baseline and 6 and 24 months after surgery by a blinded examiner. At the 6-month evaluation, both treatment procedures displayed good results with significant root coverage gain (CAF, 80.7% ± 20%; CAF + EMD, 82.8% ± 14%). A similar amount of relapse was noted at the 24-month evaluation when compared with the 6-month results (CAF, 71.0% ± 22%; CAF + EMD, 74.8% ± 16%). The use of EMD does not seem to significantly improve the results of the CAF procedure for root coverage in treatment of multiple recessions.