The arrangement of components plays a key role in the performance of complex Safety Instrumented Systems (SIS), in which a MS logic solver is interlocked with other logic solvers, to share a final element, for instance. The position of the components and the way they are utilized affects the reliability characteristics, such as the Probability of Failure on Demand (PFD), Spurious Trip Rate (STR), architectural sensitivity and model uncertainty. This case study uses quantitative and qualitative approaches to elaborate on various aspects of component arrangement in complex SIS. Numerous simplified models are analyzed; new classification is introduced for SIS components based on their response to demand; a set of guidelines are developed for MS architecture design, with a focus on component arrangement; and the use of these guidelines is demonstrated in a real-life example, where an existing turbine SIS is modified to incorporate a new over-speed protection system. The simplified models and the turbine upgrade project are also used to explain the issue of unknowns and uncertainties in reliability analysis and how these issues can be addressed in SIS architecture by optimizing component arrangement. (C) 2015 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.