Introduction: In light of recent research the efficacy of current advanced life support treatments has been questioned. Ventricular fibrillation refractory to standard therapy is a presentation which may benefit from an updated approach to management, with the b1-adrenoreceptor antagonist esmolol considered a therapy which may confer benefit. This systematic review and meta-analysis aimed to summarise the available evidence for esmolol in refractory ventricular fibrillation and identify if it may have any role in ACLS guidelines. Methods: The Cochrane Library, MEDLINE, CINAHL and EMBASE were systematically reviewed, along with trial registries and the grey literature. Studies were included in the review and subsequent meta-analysis if they examined adult patients in cardiopulmonary arrest with ventricular fibrillation refractory to at least three attempts at defibrillation and one dose of adrenaline or anti-arrhythmic therapy, who subsequently received intravenous esmolol. Results: 2,617 results were obtained with 12 full-text articles reviewed for inclusion. Ultimately, two unique results fulfilled the inclusion criteria. A total of 66 patients were included in the meta-analysis, of whom 22 received esmolol. Esmolol appears to improve to survival to hospital admission (RR 2.63, 95% CI 1.37-5.07, p=0.004), temporary (RR 2.34, 95% CI 1.09-5.02, p=0.03) and sustained ROSC (RR 2.63, 95% CI 1.37-5.07, p=0.004) and favourable neurological status at hospital discharge (RR 3.44, 95% CI 1.11-10.67, p=0.03). The use of esmolol also appeared to likely confer a benefit in survival to hospital discharge (RR 2.82, 95% CI 1.01-7.93, p=0.05). However, significant bias was observed across all outcomes and overall these results were considered to be of low to very low certainty. Conclusion: The use of esmolol in refractory ventricular fibrillation appears to improve survival to hospital admission, temporary and sustained ROSC and neurological status at hospital discharge, but not survival to hospital discharge. However, these results should be interpreted with caution in light of the limitations of included studies and the subsequent impact of these limitations on the outcomes included in the meta-analysis. Further high-quality, prospective research is required prior to recommending esmolol for use in refractory ventricular fibrillation.