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Introduction Heart failure (HF) is a complex clinical syndrome with a significant economic and health burden. While practice guidelines recommend a multidisciplinary approach in HFrEF care, the impact of pharmacist participation on HF outcomes remains inconclusive. Methods A systematic review and meta-analysis was performed and reported according to PRISMA guideline from five databases including PubMed, Embase, Cochrane, Scopus and CINAHL. Randomized controlled trials (RCTs) that evaluated pharmacist interventions compared were compared with usual care in HFrEF patients. Data were pooled using a random-effects model. The primary outcome was all-cause mortality. Secondary outcomes were all-cause hospitalization and health-related quality of life (HRQoL) at 6 months. Results Twenty-nine trials identified 6,965 predominantly HFrEF patients. The average age was 72.0 years (IQR 66.0-76.0) and 48% were men (IQR 40.0%-68.0%). The majority of trials included NYHA FC II-III with median left ventricular ejection fraction (LVEF) of 38.5% (IQR 34.5-49.5%). Pharmacist interventions were associated with a significant reduction in all-cause mortality (RR 0.74; 95% CI 0.60-0.91; p= 0.004) and all-cause hospitalizations (RR 0.86; 95% CI 0.75-0.99; p =0.034). There was a significant improvement in 4 domains of SF-36 including role physical (SMD 0.20, 95% CI 0.04 to 0.37, p=0.015), role emotional (SMD 0.17, 95% CI 0.00 to 0.33, p=0.047), mental health (SMD 0.33, 95% CI 0.17 to 0.50, p Conclusions Pharmacist interventions in HFrEF population significantly reduced all-cause mortality and all-cause hospitalizations. Several dimensions of quality of life were also improved. Integration of pharmacist into a HFrEF care team or care pathway should be strongly considered as an important element of a multidisciplinary team.