Dipyrone is a non-opioid analgesic drug used for fever and many types of pain. Due to the risk of induced agranulocytosis, it was banned in the early 1980s in several countries, but is still widely used in Brazil, Mexico, China and others. This study is a systematic review of literature focusing on the recent evidence about dipyrone safety. To this, a literature search was performed for epidemiological studies published between 2015 and 2022, in English, German, Portuguese, and Spanish languages. From the 30 articles that met the inclusion criteria, most of them consisted in observational studies (n = 27). In children, the frequency of adverse events with dipyrone is low, but can affect the renal and circulatory systems. During pregnancy, the drug doesn't seem to be related to teratogenic abnormalities. Agranulocytosis is still a matter of debate. However, the occurrence is rare, with an estimated risk of 1:1,602. In adults, dipyrone is related to several adverse effects on renal, hepatic, respiratory and epidermal systems. Thus, dipyrone seems to have a low incidence of adverse effects, but some can be considered of high severity. Especially in children, elderly and patients who need treatment for long periods, other analgesic options should be evaluated.