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Serious drug reactions can cause serious side effects, including death. A report published by Lazarou et al in 1998 showed that serious drug incidents were the 4th to 6th leading cause of death in the United States. These events may lead to drug safety issues in some cases, which require a process of problem management to resolve the problem and / or prevent similar incidents. Exploring the environment of drug safety issues based on adverse events reported at the Iranian Pharmacovigilance Center from 1999 to 2012. To discuss the consequences of the successes and failures of the disaster risk management process taken against the identified problems. Methods: All drug abuse cases detected by the Iranian Pharmacovigilance Center from 1999 to 2012 were evaluated with reports of fatal consequences. All warning letters and manuscripts published by the Center were simultaneously reviewed to obtain detailed information on the identified disasters. The World Health Organization definition was used to identify drug safety issues. Results: Out of 42036 registered cases on our site, 463 deaths were recorded. The most suspected drug for fatal side effects was ceftriaxone (100 cases). Ten different drug safety issues were identified during the study and their success or failure results were assessed. There were 112 issued warning books and 17 printed manuscripts at the same time that were closely monitored for information. Conclusion: It is necessary for national drug testing centers to have problem management plans in place. This can be helpful in reducing drug-related deaths.