Aims: We aimed to investigate the efficacy and effectiveness of pharmacist-led interventions to reduce adverse drug events (ADEs) in older people living in residential aged care facilities (RACFs). Methods: We systematically searched MEDLINE via PubMed, Embase, Cochrane Central Register of Controlled Trials and PsycINFO from their inceptions to July 2020. We investigated experimental study designs that employed a control group, or quasi-experimental studies conducted in RACFs. Results: We screened 3826 records and included 23 studies. We found seven single-component and 16 multicomponent pharmacist-led interventions to reduce ADEs in older people living in RACFs. The most frequent single-component pharmacist-led intervention was medication review. Medication review and education provision to healthcare professionals were the most common components in many pharmacist-led multicomponent interventions. Thirteen studies (56%) showed no effect, whereas ten studies (43%) reported significant reductions in ADEs following pharmacist-led interventions either as a sole intervention or as a part of a multi-component intervention. Many interventions focused on reducing the incidence of falls (39%). Conclusions: This systematic review suggests that pharmacist-led interventions have the potential to reduce the incidence of ADEs in older people living in RACFs. Medication review and educational programmes, particularly academic detailing, either as a single component or as part of multicomponent interventions were the most common approaches to reducing drug-related harm in older people living in RACFs. The lack of a positive association between interventions and ADE in many studies suggests that targeted and tailored pharmacist-led interventions are required to reduce ADEs in older people in RACFs.