The aim of this retrospective clinical study was to evaluate 2-year follow-up results following regenerative periodontal surgery for intrabony defects using enamel matrix derivative (EMD). Thirteen patients (mean age: 53 years) with a clinical diagnosis of chronic periodontitis were subjected to data analysis. A total of 25 sites with intrabony defects received regenerative therapy with EMD. Follow-up continued for a minimum of 2 years. Treatment of intrabony defects with EMD yielded a statistically significant improvement in the mean values of probing depth and gains in clinical attachment level (CAL) at 2 years compared with those at baseline (p<0.001). Sites treated with EMD demonstrated a mean CAL gain of 3.4 mm and 3.2 mm at 6 months and 2 years, respectively. No statistically significant difference in gain in CAL was found between the 6-month and 2-year results. A gain in CAL of ≥3 mm from at baseline was found in 17 sites at 2 years. This gain was achieved with minimal recession of gingival margin and was sustained over a given period of time. A trend toward a progressive increase in radiopacity, suggestive of bone-fill, was observed. In summary, treatment of intrabony defects with EMD resulted in clinically favorable outcomes. The clinical improvements obtained with regenerative therapy with EMD were maintained over a period of 2 years.