Within the licensing process of the Atucha-II pressurized heavy water reactor, the best-estimate plus uncertainty (BEPU) approach has been selected for issuing Chapter 15 of the Final Safety Analysis Report. The RELAP5-3D code developed by Idaho National Laboratory has been adopted as the best-estimate system thermal-hydraulic code to perform the accident analyses. The complexity of a nuclear power plant (NPP) and of the accident scenarios may be a challenge for a conservative analysis and may justify the choice of a BEPU approach in the licensing process. This implies two main needs: (1) the need to adopt and to prove (to the regulatory authority) an adequate quality for the computational tools and (2) the need to account for the uncertainty. The purpose of the present paper is to outline key aspects of the BEPU process aimed at the licensing of the Atucha-II (CNA-II) NPP in Argentina operated by Nucleoeléctrica Argentina (NA-SA). Among the general attributes of a methodology to perform accident analysis of a NPP for licensing purposes, the very first one should be compliance with the established regulatory requirements. A second attribute deals with the adequacy and the completeness of the selected spectrum of events that should consider the combined contributions of deterministic and probabilistic methods. The third attribute is connected to the availability of qualified tools and analytical procedures suitable for the analysis of accident conditions envisaged for the NPP of concern. The execution of the overall analysis and the evaluation of results in relation to slightly fewer than 100 scenarios revealed the wide safety margins available for the NPP of concern, which was licensed on May 29, 2014.