Background: Acute poisoning is among the most common causes of referring to the emergency departments worldwide. Since the pattern of poisoning regarding the type of component and symptoms might vary in different regions of Iran, the current study aimed at identifying the most commonly used poisoning materials causing death in Mashhad, Khorasan Razavi Province, Iran. Methodology The current cross sectional, retrospective study was conducted on all patients died from poisoning, including intentional, accidental, occupational, and criminal cases, at Imam Reza Hospital, Mashhad, Iran, in 2016. Data of patients who died from poisoning were collected from clinical records as well as forensic records including cause of death, autopsy findings, and the results of toxicological tests. Data were analyzed with SPSS version 22 using the Chi-square. Results Total mortality due to poisoning in the specific poisoning ward of Imam Reza Hospital was 71 cases in 2016, 14 cases had exclusion criteria, out of which the records of 55 cases were available. Among the 55 enrolled cases, 16 (29%) were female and 39 (71%) were male. The mean age of deceased patients was 49.84 ± 20.28 years (15-88), with the peak mortality of 45 to 60 years. Among the cases died of poisoning, 22 cases (40%) were admitted for the intentional self-poisoning and 33 cases (60%) for unintentional poisoning. According to autopsy evaluations (n = 32), the opium poisoning was the main cause of death (40.6%, n = 13). Discussion and conclusion According to the results of the current study, most of the poisoning deaths were, unintentional (unlike previous studies) and opium consumption was the main cause of death from poisoning.