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Heterotrophic plate count (HPC) constitutes a common indicator for monitoring of microbiological water quality in distribution systems (DS). This paper aims to identify factors explaining the spatiotemporal distribution of heterotrophic bacteria and model their occurrence in the distribution system. The case under study is the DS of Quebec City, Canada. The study is based on a robust database resulting from a sampling campaign carried out in about 50 DS locations, monitored bi-weekly over a three-year period. Models for explaining and predicting HPC levels were based on both one-level and multi-level Poisson regression techniques. The latter take into account the nested structure of data, the possible spatiotemporal correlation among HPC observations and the fact that sampling points, months and/or distribution sub-systems may represent clusters. Models show that the best predictors for spatiotemporal occurrence of HPC in the DS are: free residual chlorine that has an inverse relation with the HPC levels, water temperature and water ultraviolet absorbance, both having a positive impact on HPC levels. A sensitivity analysis based on the best performing model (two-level model) allowed for the identification of seasonal-based strategies to reduce HPC levels.