Failure analysis of the dam-foundation interface in concrete dams is characterized by complexity, uncertainties on models and parameters, and a strong non-linear softening behavior. In practice, these uncertainties are dealt with a well-structured mixture of experience, best practices and prudent, conservative design approaches based on the safety factor concept. Yet, a sound, deep knowledge of some aspects of this failure mode remain unveiled, as they have been offset in practical applications by the use of this conservative approach. In this paper we show a strategy to analyse this failure mode under a reliability-based approach. The proposed methodology of analysis integrates epistemic uncertainty on spatial variability of strength parameters and data from dam monitoring. The purpose is to produce meaningful and useful information regarding the probability of occurrence of this failure mode that can be incorporated in risk-informed dam safety reviews. In addition, relationships between probability of failure and factors of safety are obtained. This research is supported by a more than a decade of intensive professional practice on real world cases and its final purpose is to bring some clarity, guidance and to contribute to the improvement of current knowledge and best practices on such an important dam safety concern.