Antipsychotics have been proposed as a pharmacological alternative to prevent postoperative delirium. Nonetheless, their actual clinical benefits and harms are a matter of debate.To answer this question, we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the chosen systematic reviews, reanalyzed the data from the primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach.We identified 16 systematic reviews that included eight primary studies, all were randomized trials. We concluded the use of prophylactic antipsychotics reduces the incidence of postoperative delirium, but has no effect on the duration of hospital stay and might increase mortality.