Objective: The purpose of the present study was to compare the clinical efficiency of enamel matrix derivative (EMD) placed under a coronally advanced flap (CAF; test group), to a connective tissue graft (CTG) placed under a CAF (control group), in patients with multiple recession defects. Method and Materials: Twelve patients with multiple Miller's Class I or II gingival recessions in contralateral quadrants of the maxilla were selected. The primary outcome variable was the change in depth of the buccal recession (REC), at 6 months (T6) after surgery. The secondary outcome parameters included the clinical attachment level (CAL), the probing pocket depth (PPD), and the width of keratinized gingiva (WKT) apical to the recession. Recession defects were randomly divided to the test or control group by using a computer-generated randomization list. Data were analyzed within the frame of Mixed Linear Models with the ANOVA method. Results: There were no statistically significantly differences observed between test and control groups in regards with the depth of buccal recession with a mean REC of 1.82 mm (CTG) and 1.72 mm (EMD) respectively. Similarly the mean PPD value was 1.3 mm for both groups at T6, while the respective value for CAL was 1.7 mm (EMD) and 1.8 mm (CTG). Statistically significant differences were observed only for the WKT, which were 3.0 mm and 3.6 mm for the test and control groups respectively (P .001) at T6. Conclusion: The use of EMD in conjunction with a CAF resulted in similar results as compared to the CTG plus CAF. Keywords: enamel matrix derivative (Emdogain), gingival recessions, root coverage