OBJECTIVE:Alert fatigue limits the effectiveness of medication safety alerts, a type of computerized clinical decision support (CDS). Researchers have suggested alternative interactive designs, as well as tailoring alerts to clinical roles. As examples, alerts may be tiered to convey risk, and certain alerts may be sent to pharmacists. We aimed to evaluate which variants elicit less alert fatigue. MATERIALS AND METHODS:We searched for articles published between 2007 and 2017 using the PubMed, Embase, CINAHL, and Cochrane databases. We included articles documenting peer-reviewed empirical research that described the interactive design of a CDS system, to which clinical role it was presented, and how often prescribers accepted the resultant advice. Next, we compared the acceptance rates of conventional CDS-presenting prescribers with interruptive modal dialogs (ie, "pop-ups")-with alternative designs, such as role-tailored alerts. RESULTS:Of 1011 articles returned by the search, we included 39. We found different methods for measuring acceptance rates; these produced incomparable results. The most common type of CDS-in which modals interrupted prescribers-was accepted the least often. Tiering by risk, providing shortcuts for common corrections, requiring a reason to override, and tailoring CDS to match the roles of pharmacists and prescribers were the most common alternatives. Only 1 alternative appeared to increase prescriber acceptance: role tailoring. Possible reasons include the importance of etiquette in delivering advice, the cognitive benefits of delegation, and the difficulties of computing "relevance." CONCLUSIONS:Alert fatigue may be mitigated by redesigning the interactive behavior of CDS and tailoring CDS to clinical roles. Further research is needed to develop alternative designs, and to standardize measurement methods to enable meta-analyses.