The aim of this clinical study was to evaluate the coverage of gingival recession defects with enamel matrix derivatives (EMD) with or without a connective tissue graft (CTG). Twenty-five patients (16 female, 9 male) from 16 to 58 years of age (mean: 32.2; SD: 11.2) with 92 gingival recessions (Miller Class I and II) and with at least 4.0 mm of clinical attachment loss were treated with a modified surgical technique for root coverage by CTG with EMD (45 recession defects) or EMD only (47 recession defects). Vertical recession depth, probing depth, clinical attachment level, dehiscence depth, width of keratinized gingiva (vertical), and recession coverage were recorded before surgery (baseline) and at 12 and 24 months. The average presurgical recession depth was 4.4 mm (SD: 1.3) with EMD and CTG versus 3.2 mm (SD: 1.1) with EMD only. Both treatment modalities led to a significant decrease in recession and a gain in attachment. Mean root coverage 12 months postoperatively was 92.7% (SD: 13.5) (EMD and CTG) versus 96.3% (SD: 11.5) (EMD only). Compared to the mean root coverage of recession after 24 months, the change was not significant. The results confirmed that the applied modified surgical techniques are safe and predictable, with better clinical outcomes at the donor and recipient sites. (Int J Periodontics Restorative Dent 2008;28:497–507.)