AIM The increasing popularity of randomized-controlled trials (RCTs) has raised the issue of their quality. Frequently overlooked are the differences between superiority and equivalence trials. The purpose of this study was to apply specific methodological criteria to evaluate the quality of active-control trials using studies that compared guided tissue regeneration (GTR) with enamel matrix derivatives (EMD). MATERIALS AND METHODS Seven RCTs were identified in the literature. Standard methodological criteria and seven additional criteria for trials using active-control groups were used to evaluate the quality of the seven RCTs. RESULTS Two trials were considered as superiority trials. The remaining five provided no clear statement of their research aim. However, two claimed that EMD and GTR were equally effective, because their results failed to show a significant difference between EMD and GTR. Most trials did not meet the majority of the design criteria. CONCLUSIONS The general lack of compliance with quality criteria might place doubt on the value of these trials and may render any conclusions questionable. It is therefore important to distinguish clearly between superiority trials and equivalence trials, and to incorporate appropriate additional criteria in the design of future RCTs with active-control groups.