The Early Start Denver Model (ESDM) has been gaining popularity as a comprehensive treatment model for children ages 12 to 60 months with autism spectrum disorders (ASD). This article evaluates the research on the ESDM through an analysis of study design and purpose; child participants; setting, intervention agents, and context; density and duration; and overall research rigor to assist professionals with knowledge translation and decisions around adoption of the practices. Ten research studies are included in this systematic review. Findings indicate variability in methodologies, participant and intervention characteristics, and research rigor. The ESDM shows promise as an evidence-based practice for young children with ASD and there is preliminary evidence to support implementation of the ESDM. Children are progressing with ESDM intervention and fidelity of implementation has been achieved in community-based settings. The extent to which child improvements are due to the ESDM intervention alone is not fully known. Additional studies are needed including replication by independent researchers to determine "active ingredients," level of effectiveness, and whether the ESDM is better than other treatment options. This review highlights research opportunities to expand professionals' knowledge of the ESDM's effectiveness. Clinical decisions around adoption and feasibility of implementation in communities will be enhanced with greater knowledge and understanding.