Introduction: Clinical decision support (CDS) has been implemented in many clinical settings in order to improve decision-making. Their potential to improve diagnostic accuracy and reduce unnecessary testing is well documented; however, their effectiveness in impacting physician practice in real world implementations has been limited by poor physician adherence. The objective of this systematic review and meta-regression was to establish the effectiveness of CDS tools on adherence and identify which characteristics of CDS tools increase physician use of and adherence. Methods: A systematic review and meta-analysis was conducted. MEDLINE, EMBASE, PsychINFO, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews were searched from inception to June 2017. Included studies examined CDS in a hospital setting, reported on physician adherence to or use of CDS, utilized a comparative study design, and reported primary data. All tool type was classified based on the Cochrane Effective Practice and Organization of Care (EPOC) classifications. Studies were stratified based on study design (RCT vs. observational). Meta-regression was completed to assess the different effect of characteristics of the tool (e.g. whether the tool was mandatory or voluntary, EPOC classifications). Results: A total of 3,359 candidate articles were identified. Seventy-two met inclusion criteria, of which 46 reported outcomes appropriate for meta-regression (5 RCTs and 41 observational studies). Overall, a trend of increased CDS use was found (pooled RCT OR: 1.36 [95% CI: 0.97-1.89]; pooled observational OR: 2.12 [95% CI: 1.75-2.56]).When type of tool is considered, clinical practice guidelines were superior compared to other interventions (p=.150). Reminders (p=.473) and educational interventions (p=.489) were less successful than other interventions. Multi-modal tools were not more successful that single interventions (p=.810). Lastly, voluntary tools may be supperior to than mandatory tools (p=.148). None of these results are statistically significant. Conclusion: CDS tools accompanied by a planned intervention increases physician utilization and adherence to the tool. Meta-regression found that clinical practice guidelines had the biggest impact on physician adherence although not statistically significant. Further research is required to understand the most effective intervention to maximize physician utilization of CDS tools.