Objective: The main objective of this study was to evaluate the clinical effectiveness of platelet-rich fibrin membrane used in combination with a coronally advanced flap (CAF) and to compare it with the use of an enamel matrix derivative (EMD) in combination with a coronally advanced flap in gingival recession treatment. Materials and methods: 20 split-mouth cases of maxillary anterior teeth or bicuspids presenting with Miller Class I or II gingival recession were treated with a CAF combined with a platelet-rich fibrin membrane (PRF group) or with EMD (EMD group) placed under a CAF. The following parameters were measured at baseline and at 12 months post treatment: gingival recession (GR), apicocoronal width of the keratinized tissue (WKT), and probing depth (PD). Results: Complete root coverage in the PRF group was 65% (13 out of 20 recessions) and 60% in the EMD group (12 out of 20 recessions). GR was 4.10 ± 1.05 mm in the PRF group and 3.90 ± 1.00 mm in the EMD group at baseline, and 1.05 ± 0.45 mm in the PRF group and 1.15 ± 0.65 mm in the EMD group at 12 months. The difference observed between the two groups at 12 months was statistically significant. Average root coverage was 70.5% in the EMD group and 72.1% in the PRF group. WKT was 1.30 ± 0.56 mm in the EMD group and 1.45 ± 0.86 mm in the PRF group at baseline, and 1.90 ± 0.81 mm in the EMD group and 1.62 ± 0.28 mm in the PRF group at 12 months. The difference observed between the two groups at 12 months was not statistically significant. Twelve-month changes in PD were not significantly different between the two groups. The pain intensity was statistically different between groups for the first 5 days, favoring the PRF group. Conclusions: The present study did not succeed in demonstrating any clinical advantage of the use of PRF compared to EMD in the coverage of gingival recession with the CAF procedure. The EMD group showed a higher success rate in increasing WKT than did the PRF group.