A methodology is proposed to design emergency systems using Probabilistic Safety Assessment (PSA). It was used to design mitigation systems in the case of the formation of a toxic cloud due to an uncontrolled leakage of concentrated sulfuric acid in the second section of the General Atomics S I cycle of a hydrogen production plant. Mitigation systems based on the isolation of a possible leak, the neutralization of a puddle of sulfuric acid and finally the flushing of that puddle were proposed and later analyzed with PSA. Many scenarios were taken into account to determine design changes and their impact on the probability of failure of the systems. Finally, the information produced in the PSA was used to provide feedback to optimize the design of the toxic cloud mitigation systems. The specific recommendations from the study suggest several design changes based on the PSA sensitivity runs. The results include optimized isolation and neutralization systems that will maintain the frequency of toxic cloud formation below 1.0E - 09 per year, which is only 16% of the frequency calculated for the original design based only on process engineering. (C) 2010 Professor T. Nejat Veziroglu. Published by Elsevier Ltd. All rights reserved.