Background and Aims <p>The optimal stenting strategy for malignant hilar biliary obstruction (MHBO) remains controversial, with debate about the choice between unilateral (UL) and bilateral (BL) stenting. This meta-analysis compares the safety and efficacy of UL and BL stenting in treating MHBO.</p> Methods <p>We searched PubMed, Embase, Scopus, and others until February 2024 for studies comparing UL and BL stenting for MHBO. Technical and clinical success were our primary outcomes. Analyses calculated pooled risk ratios (RR) or hazard ratios (HR) with 95% confidence intervals using random-effects models.</p> Results <p>A total of 21 studies (5 RCTs and 16 observational studies) involving 2567 patients (1224 in UL and 1343 in BL group) were included in this meta-analysis. UL showed higher clinical success rates RR (0.97, 95% CI 0.94–0.99, <i>p</i> = 0.01) and similar technical success rates (1.01, 95% CI 1.00–1.03, <i>p</i> = 0.09) than UL. Whereas BL stenting was associated with higher early and similar late adverse event rates (0.59, 95% CI 0.45–0.77, <i>P</i> = 0.0001 and 0.87, 95% CI 0.74–1.03, <i>p</i> = 0.11). Significant differences in stent patency HR (0.76, 95% CI 0.66–0.87, <i>p</i> = 0.0001) and overall survival (0.77, 95% CI 0.68–0.87, <i>p</i> &lt; 0.0001) were observed between the two stenting procedures. Subgroup analysis showed that endoscopic BL metal stenting showed improved results.</p> Conclusions <p>BL stenting for MHBO improves stent patency and survival over UL stenting, as well as better results combined with chemotherapy, but it involves the high risk of early adverse events.</p> Trial Registration <p>This systematic review and meta-analysis was registered at PROSPERO (<a href="https://www.crd.york.ac.uk/PROSPERO/">https://www.crd.york.ac.uk/PROSPERO/</a>) with registration number CRD42024523434.</p>