Introduction: Although previous meta-analyses have explored the efficacy and safety of direct oral anticoagulants (DOAC) compared to warfarin in patients with atrial fibrillation (AFib) and liver disease, recent studies and emerging data necessitate a re-evaluation of the topic. Therefore, we con ducted an updated meta-analysis to incorporate the latest evidence and provide a more comprehensive understanding of the literature. This meta-analysis aimed to assess the safety and efficacy of DOAC in patients diagnosed with AFib and liver disease. Methods: Following PRISMA guidelines, this meta-analysis is registered with PROSPERO (2024 CRD42024584964). A detailed search up to August 2024 was conducted for the studies comparing DOAC with warfarin. The quality of the included observational studies was evaluated using the Risk of Bias in Non-randomized Studies – of Interventions (ROBINS-I) tool. Results: This meta-analysis included 53,224 participants with AFib and liver disease. The use of DOAC, in comparison to warfarin, was significantly linked to a lower risk of all-cause mortality (HR = 0.77; 95% CI: 0.60–0.98; p = 0.04) and a decreased occurrence of intracranial haemorrhage (HR = 0.49; 95% CI: 0.40–0.59; p < 0.00001). However, other outcomes did not demonstrate statistically significant differences. Conclusions: Recent studies indicate that DOAC are at least non-inferior to warfarin concerning efficacy and safety of patients with AFib and liver disease.