Ethylene oxide is widely used as a sterilizing agent for medical and food applications and products. However, due to its broad range of flammability (2.6 % to 100 %) in air, this gas presents a particularly serious explosion hazard, which is compounded by extremely stringent and ever increasing requirements for pollution control equipment. Many emission control devices contain potential ignition sources, such as open flames, that could trigger an explosion. Engineering controls and safety interlocks are therefore critical to prevent explosions during abnormal operation and process upsets. This paper describes an investigation of a large explosion that caused extensive damage at a sterilization facility in the United States in August, 2004. The incident occurred as workers were attempting to troubleshoot one of their sterilization chambers and consequently bypassed safety interlocks while evacuating the gas. This allowed a flammable mixture to enter an ethylene oxide destruction unit (abator), which utilized an open flame to preheat waste gases before they passed through a catalytic oxidizer bed. The resulting deflagration propagated through the ductwork and back into the sterilization chamber, which exploded. The authors present the lessons learned from this incident through their direct involvement with the incident investigation as well as a review of previous, similar incidents investigated by the United States Environmental Protection Agency (EPA). The root cause and contributory factors for this explosion are discussed and recommendations provided on how similar incidents might be avoided in the future. One of the authors serves on the NFPA committee responsible for publishing the standard on safe storage, handling and use of ethylene oxide, and the paper concludes with an regulatory and industry perspective on alternative designs and equipment that could have prevented the explosion or vented/diverted the overpressure in order to lessen the damage to the workers and the facility.