This meta-analysis aims to compare the effect of the application of enamel matrix derivative (EMD) used alone with that of its use in combination with alloplastic materials in the treatment of periodontal intrabony defects. Relevant studies were retrieved from PubMed, the Cochrane Library, and Embase through November 2015. The main clinical outcomes were pocket probing depth (PPD) reduction, clinical attachment level (CAL) gain, gingival recession (REC) increase, and defect fill gain. Two separate meta-analyses were performed according to the length of follow-up. Nine articles were included. The results demonstrated that in the short-term follow-up group (≤ 1 year), in terms of PPD reduction (P .05) and REC increase (P .05), the application of an EMD combined with alloplastic materials provided advantages compared to EMD used alone. For CAL gain (P = .17) and gain of defect fill (P = .07), no significant differences were observed. In the long-term follow-up group (> 1 year), no significant differences in terms of REC increase (P = .05) were found between the groups, but combined therapy exhibited an advantage in terms of PPD reduction (P .05), CAL gain (P .05), and gain in defect fill (P .05). Within its limitations, this meta-analysis indicated that the additional benefit of combined therapy in the treatment of periodontal intrabony defects compared with EMD used alone cannot be proven.