Background Antibiotic resistance poses a considerable public health threat, with data-driven stewardship a main prevention measure. While quantifying antibiotic consumption is a key component of antibiotic stewardship programmes, the choice of denominator for calculating this metric can impact comparative analyses and trend evaluations substantially, influencing targeted stewardship interventions. Aim We aim to evaluate how using hospital sector-specific antibiotic consumption rate denominators at country level impacts country rankings and trends, addressing the limitations of the commonly used 'defined daily doses (DDD) per 1,000 inhabitants per day' metric. Methods Hospital antibiotic consumption data from ESAC-Net and denominator data from Eurostat (‘inhabitants,’ ‘bed-days’ and ‘discharges’) for 2017–2021 were used to calculate hospital antibiotic consumption rates for 24 reporting European Union/ European Economic Area (EU/EEA) countries. Countries were ranked by their consumption rates and trends were analysed to assess the effects of using different denominators. Results Country rankings and 5-year trend analyses varied depending on the denominator used. Antibiotic consumption rates were more similar when using hospital activity-based denominators ‘bed-days’ and ‘discharges’ compared with the population-based ‘inhabitants’ denominator. Differences in country rankings and trends were also seen among rates derived using ‘bed-days’ and ‘discharges’. Conclusion The study underscores the importance of using hospital activity-based denominators such as ‘bed-days’ and ‘discharges’ when evaluating hospital antibiotic consumption. ESAC-Net’s historical reliance on only ‘DDD per 1,000 inhabitants per day’ is challenged, advocating for the use of multiple hospital activity-based denominators. Corresponding hospital activity denominators for ESAC-Net data will more effectively inform national hospital antibiotic stewardship interventions.