Treatment of intrabony periodontal defects with an enamel matrix derivative (EMD) has been shown to predictably enhance periodontal regeneration. The aim of the present study was to evaluate the 4-year results following treatment of intrabony defects with EMD. Thirty-three patients with a total of 46 intrabony defects were treated. Each patient exhibited at least one intrabony defect with a probing depth >= 6 mm as identified by probing and on radiographs. The following clinical parameters were evaluated prior to and 1 and 4 years after treatment: probing depth, recession of the gingival margin, and clinical attachment level. The primary oucome variable was clinical attachment. Mean probing depth was reduced from 8.1 ± 1.8 mm to 3.8 ± 1.2 mm at 1 year and to 4.0 ± 1.2 mm at 4 years. No statistically significant differences were found between the mean probing depth 1 and 4 years postoperative. At 1 year, the mean recession increased from 1.9 ± 1.5 mm to 3.2 ± 1.8 mm; at 4 years, it was 2.8 ± 1.2 mm, a statistically significant improvement compared to the 1-year results, but still significantly increased compared to the baseline. The mean attachment level changed from 10.0 ± 2.4 mm to 7.0 ± 2.1 mm at 1 year and 6.8 ± 1.9 mm at 4 years (no statistically significant difference). The clinical improvements obtained following treatment with EMD can be maintained over a 4-year period.