Background: Older people are particularly vulnerable to medication errors and adverse drug events (ADEs) due to polypharmacy and age-related physiological changes. Clinical decision support systems (CDSS) presents itself as a potential solution for clinicians, but their effectiveness in care for older people remains uncertain.

Objectives: To evaluate the impact of CDSS on reducing potentially inappropriate medications (PIMs) and improving medication safety amongst older people. DESIGN AND

Setting: This was a systematic review of randomized controlled trials (RCTs) evaluating CDSS interventions in older populations (aged 65 or older).

Methods: A comprehensive search was conducted in OVID Medline, Embase, and Cochrane Library from inception to April 2025. Eligible studies were RCTs assessing CDSS in reducing PIM use and ADEs amongst older people. Data on medication safety outcomes (PIM, deprescription and ADEs) were extracted. The findings were narratively synthesized, and the certainty of evidence was evaluated using the GRADE framework. The Cochrane Risk-of-Bias 2 tool was also applied.

Results: A total of 16 RCTs (comprising 135,108 participants) were included. CDSS significantly reduced PIM initiation by up to 18% (moderate certainty) and improved deprescription rates, with intervention groups achieving 55.4% PIM discontinuation. However, CDSS had inconsistent effects on ADEs (low certainty).

Conclusions: CDSS improved prescribing practices by reducing inappropriate medication use in older people. However, its impact on ADEs was less evident. Implementation challenges such as clinician adherence, alert fatigue and system usability must be addressed to optimize CDSS effectiveness in care for older people. Further research is needed for long-term evaluation and refinement of CDSS.