BACKGROUND Computerized decision support systems have raised a lot of hopes and expectations in the field of order entry. Although there are numerous studies reporting positive impacts, concerns are increasingly high about alert fatigue and effective impacts of these systems. One of the root causes of fatigue alert reported is the low clinical relevance of these alerts. OBJECTIVE The objective of this systematic review was to assess the reported positive predictive value (PPV), as a proxy to clinical relevance, of decision support systems in computerized provider order entry (CPOE). METHODS A systematic search of the scientific literature published between February 2009 and March 2015 on CPOE, clinical decision support systems, and the predictive value associated with alert fatigue was conducted using PubMed database. Inclusion criteria were as follows: English language, full text available (free or pay for access), assessed medication, direct or indirect level of predictive value, sensitivity, or specificity. When possible with the information provided, PPV was calculated or evaluated. RESULTS Additive queries on PubMed retrieved 928 candidate papers. Of these, 376 were eligible based on abstract. Finally, 26 studies qualified for a full-text review, and 17 provided enough information for the study objectives. An additional 4 papers were added from the references of the reviewed papers. The results demonstrate massive variations in PPVs ranging from 8% to 83% according to the object of the decision support, with most results between 20% and 40%. The best results were observed when patients' characteristics, such as comorbidity or laboratory test results, were taken into account. There was also an important variation in sensitivity, ranging from 38% to 91%. CONCLUSIONS There is increasing reporting of alerts override in CPOE decision support. Several causes are discussed in the literature, the most important one being the clinical relevance of alerts. In this paper, we tried to assess formally the clinical relevance of alerts, using a near-strong proxy, which is the PPV of alerts, or any way to express it such as the rate of true and false positive alerts. In doing this literature review, three inferences were drawn. First, very few papers report direct or enough indirect elements that support the use or the computation of PPV, which is a gold standard for all diagnostic tools in medicine and should be systematically reported for decision support. Second, the PPV varies a lot according to the typology of decision support, so that overall rates are not useful, but must be reported by the type of alert. Finally, in general, the PPVs are below or near 50%, which can be considered as very low.