The influences of natural organic matter (NOM) and bacteriological characteristics on the biological stability of water were investigated in a full-scale drinking water treatment plant. We found that prechlorination decreased the hydrophobicity of the organic matter and significantly increased the high-molecular-weight (MW) dissolved organic matter, such as biopolymers and humic substances. High-MW organic matter and structurally complex compounds are known to be relatively slowly biodegradable; however, because of the prechlorination step, the indigenous bacteria could readily utilise these fractions as assimilable organic carbon. Sequential coagulation and sedimentation resulted in the substantial removal of biopolymer (74%), humic substance (33%), bacterial cells (79%), and assimilable organic carbon (67%). Rapid sand and granular activated carbon filtration induced an increase in the low-nucleic-acid content bacteria; however, these bacteria were biologically less active in relation to enzymatic activity and ATP. The granular activated carbon step was essential to securing biological stability (the ability to prevent bacterial growth) by removing the residual assimilable organic carbon that had formed during the ozone treatment. The growth potential of Escherichia coli and indigenous bacteria were found to differ in respect to NOM characteristics. In comparison with E. coli, the indigenous bacteria utilised a broader range of NOM as a carbon source. Principal component analysis demonstrated that the measured biological stability of water could differ, depending on the NOM characteristics, as well as on the bacterial inoculum selected for the analysis.