The current work is devoted to problems connected with application of CFD tools for safety analysis of large-scale industrial structures. With the aim to preserve conservatism of overall process of multi-stage procedure of such analysis special efforts are required. A strategy which has to lead to obtaining of reliable results in CFD analysis is discussed. Different aspects of proposed strategy, including: adequate choice of physical and numerical models, procedure of validation simulations, and problem of 'under-resolved' simulations are considered. For physical phenomena which could cause significant uncertainties in the course of scenario simulation, an approach, which complements CFD simulations by application of auxiliary criteria, is presented. Physical basis and applicability of strong flame acceleration and detonation-to-deflagration transition criteria are discussed. In concluding part two examples of application of presented approach for nuclear power plant and workshop cell for hydrogen driven vehicles are presented.