Introduction <p>Unresolved drug-related problems may cause preventable medication-related harm and contribute to hospital readmissions. Comprehensive medication reviews conducted by clinical pharmacists are used to identify and address drug-related problems in hospital settings. However, the clinical relevance of drug-related problems that remain unresolved after identification, particularly in relation to hospital readmissions, remains unexplored.</p> Aim <p>To examine the association between unresolved drug-related problems and 6-month all-cause hospital readmission, and to describe drug-related problem identification, intervention acceptance, and resolution during pharmacist-led comprehensive medication reviews.</p> Method <p>A retrospective observational study was conducted in a tertiary hospital (2019–2022). Inpatients and outpatients referred by doctors for a pharmacist-led comprehensive medication review with ≥ 1 identified drug-related problem were included. The primary outcome was all-cause hospital readmission within 6&#xa0;months following the medication review. Additional process measures included doctors’ acceptance of pharmacists’ recommendations, drug-related problem resolution status assessed based on follow-up documentation at 6&#xa0;months, and the number of additional drug-related problems identified by pharmacists beyond those detected by doctors.</p> Results <p>A total of 177 patients undergoing 185 comprehensive medication reviews were included, in whom 505 drug-related problems were identified (mean 2.7 per review, standard deviation 2.0). Clinical pharmacists identified 73.9% of all drug-related problems and proposed interventions for 88.9% of them. Overall, 70.2% of pharmacists’ recommendations were accepted by doctors. In a patient-level multivariable analysis adjusting for age, sex, comorbidities, medication count, total drug-related problem count, and the number of comprehensive medication reviews, the presence of any unresolved drug-related problems (OR = 4.02, 95% CI: 1.12–14.39, <i>p</i> = 0.033) and the number of unresolved drug-related problems (OR = 1.74, 95% CI: 1.10–2.74, <i>p</i> = 0.017) were independently associated with higher readmission risk, as was comorbidity count (OR = 1.47, 95% CI: 1.01–2.15, <i>p</i> = 0.046).</p> Conclusion <p>In this retrospective study, the presence of unresolved drug-related problems following pharmacist-led comprehensive medication reviews was independently associated with four-fold higher odds of hospital readmission within 6&#xa0;months. These findings highlight unresolved drug-related problems as a strong, independent marker of increased readmission risk. Prospective studies are needed to determine whether interventions that successfully resolve DRPs can causally reduce readmissions.</p>