Although pharmacist-led interventions in anticoagulant (AC) therapy are widely accepted, there is a lack of evidence comparing their effectiveness to usual care in terms of AC therapy appropriateness and clinical outcomes. We aimed to estimate the comparative effectiveness of pharmacist-led interventions on the appropriateness and clinical outcomes of AC therapy. Adhering to the PRISMA guidelines, we searched PubMed, EMBASE, and Scopus databases to identify randomised controlled trials and quasi-experimental and cohort studies published between 2010 and 2023. A random-effects model was used to calculate pooled intervention effects. We assessed heterogeneity (using Higgins' I2 and Cochran's Q) and publication bias (using Egger's test, the trim-and-fill method and visualisation of the funnel plot). In total, 35 studies involving 10374 patients in the intervention groups and 11840 in the control groups were included. The pharmacist-led interventions significantly improved the appropriateness of AC therapy (odds ratio [OR]: 3.43; 95% confidence interval [CI]: 2.33-5.06, p<0.01). They significantly decreased total bleeding (relative risk [RR]: 0.75, 95% CI: 0.58-0.96, p=0.03) and hospitalisation or readmission (RR: 0.64, 95% CI: 0.41-0.99, P=0.04). However, the impact of the pharmacist-led interventions on thromboembolic events (RR: 0.69, 95% CI: 0.46-1.02, p=0.07) and mortality (RR: 0.76, 95% CI: 0.51-1.13, p=0.17) were not significant. Pharmacist-led interventions demonstrated superior outcomes in optimising AC therapy compared to usual care. Further research is needed to evaluate pharmacist-led interventions' cost-effectiveness and long-term sustainability.PROSPERO registration number CRD42023487362.