In 2007, the American Petroleum Institute (API 521/ISO 23251) published guidance on the use of High Integrity Protective Systems (HIPS) to mitigate overpressure scenarios. A natural extension of HIPS is to use system design and operating discipline to mitigate overpressure scenarios where use of fully instrumented protection layers or conventional relief devices is neither practical nor effective. In Dow, this approach is referred to as Alternate Overpressure Protection (AOP). System design (HIPS or AOP) is commonly used to mitigate overpressure scenarios when: (1) a conventional pressure relief device (PRD) is not practical or effective, (2) a conventional PRD will not be reliable or (3) a conventional PRD will work but is not cost effective. HIPS or AOP can also be used to reduce the required relief size by limiting the operating window of the process. The purpose of this article is to provide several practical examples on the use of HIPS and AOP and to describe some of the challenges and associated strategies to ensure successful implementation and sustained process safety performance. (c) 2013 American Institute of Chemical Engineers Process Saf Prog 32: 248-254, 2013