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Background The Diagnosis-Related Groups (DRGs) and Diagnosis-Intervention Packet (DIP) payment models aim to enhance healthcare efficiency, yet primary hospitals struggle with rational drug use under cost-control pressures. Pharmaceutical information management systems (PIMS) offer a potential solution, yet evidence from resource-limited settings remains limited. We evaluated whether a multifaceted intervention incorporating PIMS can improve drug use rationality and financial performance under DRGs/DIP in a primary hospital setting. Methods A quasi-experimental study with historical controls compared pre-intervention (January-December 2022) and post-intervention (January-December 2023) data from a primary hospital in Sichuan Province, China. The intervention comprised multidisciplinary team coordination, real-time clinical decision support, pharmacist-led ward rounds, training programs, and clinical pathway optimization. Outcomes included drug costs, antimicrobial use intensity (defined daily doses [DDD]/100 bed-days), prescription rationality rates, and DRG financial balance. Due to data aggregation at the hospital level, segmented regression analysis was not feasible; independent t-tests were used for pre-post comparisons. Results Post-intervention, average outpatient drug costs decreased significantly (33.48±3.67 vs. 39.29±5.52 yuan, p=0.006), and inpatient antimicrobial use intensity declined from 48.97±6.02 to 43.71±3.06 DDD/100 bed-days (p=0.013). Prescription review compliance improved from 93.67% to 97.50% (p<0.001). DRG settlement shifted from a loss of ¥394,800 to a surplus of ¥198,700. However, without adjustment for case-mix changes, seasonal variation, or concurrent policy reforms, causal attribution remains uncertain. Conclusions The multifaceted intervention was associated with improved drug use indicators and financial performance. These findings suggest potential benefits of integrating PIMS with pharmacist-led interventions in primary care, though methodological limitations preclude strong causal inference. Further research employing rigorous quasi-experimental methods across multiple sites is warranted.