The paper describes briefly a best estimate plus uncertainty analysis (BE+UA) methodology and presents its prototyping application to the power pulse phase of a limiting large Loss-of-Coolant Accident (LOCA) for a CANDU 6 reactor fuelled with CANFLEX® fuel. The methodology is consistent with and builds on world practice [1], [2]. The analysis is divided into two phases to focus on the dominant parameters for each phase and to allow for the consideration of all identified highly ranked parameters in the statistical analysis and response surface fits for margin parameters. The objective of this analysis is to quantify improvements in predicted safety margins under best estimate conditions.