Objectives: Although the incidence of drug-induced-anaphylaxis is increasing, there is a major gap in the literature regarding the economic burden of drug induced anaphylaxis (DIA). This systematic review evaluates published data related to the economic burden of DIA in order to gather evidence-based data to implement preventive cost saving measures with the attempt to reduce the burden of these conditions. Method: We searched MEDLINE, Science Direct, Cochrane, Scielo and Lilacs websites, databases for manuscripts concerning the term “drug-induced anaphylaxis” AND “cost” or “economic burden”, with no language restrictions. We screened studies, extracted data and assessed the risk for bias independently in duplicate. Results: From all 248 publications, four reports were considered eligible for this study. All articles covered direct costs and one covered indirect cost. Three articles were related to etiological investigation of DIA and/or management of anaphylaxis and one was related to desensitization. All the studies used different cost parameters to access the direct cost. The cost of investigations was determined in two of the studies (288$–2292.95$, mean 1290.48$) and in one article the desensitization cost was considered. The main studied variables for this cost were personnel, allergy screening procedures, medical consumables and space cost. Number of emergency room visits/hospitalizations, emergency kits, transports in ambulance were considered in two of the articles ($529.6–$3125, mean $1827.3). The mean indirect cost was analysed in one study and was based on a mean absenteeism of 3 days per DIA corresponding to $381.2. Conclusions: The DIA economic burden, considering both management of the acute phase and etiological investigations, is high. However, publications in the field are scarce with limited and heterogeneous data. Beyond reviewing the publish data, we were able to identify variables that, if correctly managed, can reduce the economic burden of DIA. The evidence presented here highlights the need of optimization of health care patients to patients suffering from DIA.