Optimal postoperative pain management is a prerequisite for enhancing functional recovery after surgery. However, many studies assessing analgesic interventions have limitations. Consequently, further improvements in study design are urgently needed. In this focused editorial, we critically review prevalent trial designs and outcome measures including treatment-related adverse events evaluating analgesic interventions. Novel clinical trial designs should improve efficiency and enhance the likelihood of detecting relevant treatment effects. Cohort and database studies using propensity score matching and directed acyclic graphs could provide real-world generalisable information. Procedure-specific and patient-specific trials should allow identification of subpopulations most likely to benefit from a particular intervention after a specific surgical procedure and thus ascertain optimal analgesic strategies in challenging populations.