Objective To describe the best evidence on the effectiveness of technology-based learning tools designed to improve knowledge of health care providers about clinical practice guidelines (CPGs). Methods We conducted a systematic review, searching MEDLINE, Embase, and CINAHL from inception to July 2018. Included studies investigated the effectiveness of any technology-based learning tools developed to improve knowledge of health care providers about CPGs. We used a 2-phase screening process to determine eligibility. Pairs of reviewers critically appraised relevant studies using the Scottish Intercollegiate Guidelines Network checklist for randomized controlled trials or the National Institutes of Health checklist for pre- and postintervention trials. Evidence from internally valid studies was described using a best-evidence summary. We conducted a sensitivity analysis to determine whether results varied according to methodological quality. Results Twenty-five of 8321 articles met our selection criteria. Six studies had a low risk of bias and were included in this review. Spaced education was associated with improvement in knowledge; however, its effectiveness relative to other interventions is unknown. Module-based online educational interventions were associated with improvement in knowledge of CPGs; however, they may not be more effective than paper-based self-learning or in-person workshops. The sensitivity analysis determined that the evidence was similar between the high and low risk of bias studies. Conclusion Module-based- and spaced-education interventions may be beneficial for improving health care providers' knowledge of CPGs; however, much of the evidence toward their use is preliminary.