Objectives: The aim of this 5-year long-term split-mouth design randomized clinical trial (RCT) was to evaluate the effectiveness of coronally advanced flap (CAF) alone versus coronally advanced flap with connective tissue graft (CAF + CTG) in the treatment of single and multiple Miller Class I and II gingival recession defects. Patients and Methods: Fifty-four subjects with 244 bilateral single and multiple Miller Class I and II recession defects were treated with CAF procedure on one and with CAF + CTG procedure on the other side of the mouth. Clinical measurements (gingival recession depth, REC; keratinized tissue width, KT; complete root coverage, CRC and percentage of root coverage, PRC) were evaluated before surgery and after six, 12, 24 and 60 months post-operatively. Results: There was a significant reduction of REC and increase in KT after surgery in both groups. CAF + CTG showed significantly better results in the treatment of single and multiple Miller Class I and II gingival recession defects for all evaluated clinical parameters and in all observed follow-up periods. Miller Class I defects showed better results than Miller Class II defects regardless of the surgical procedure used. Conclusion: Both surgical procedures were effective in the treatment of single and multiple Miller Class I and II gingival recession defects. CAF + CTG procedure provided better long-term outcome than CAF alone. Long-term stability of gingival margin was less predictable for Miller Class II recession defects compared to Class I.