Comparisons between antimicrobial usage (AMU) in humans and food-producing animals are regularly made. The accuracy of such comparisons depends on the indicators used to quantify AMU. Indicators for AMU quantitatively relate use data (the numerator) to population data (the denominator). The denominator should be a proxy for the population at risk in a certain period when comparing the exposure of different populations to antimicrobials. Denominators based on numbers of animals slaughtered, such as the commonly used population correction unit, do not consider the time at risk of antimicrobial treatment. Production-based indicators underestimate animal AMU. Additionally, production-based indicators are fundamentally different from indicators used to quantify human AMU. Using such indicators to compare human and animal AMU therefore leads to biased results. More caution should be taken in selecting the indicator to quantify AMU when comparing AMU in food-producing animals and humans