BACKGROUND: Whether beta-blockers should be continued during hospitalization for acute decompensated heart failure (ADHF) remains uncertain. OBJECTIVES: The objective of the study was to conduct a systematic review on continuation vs discontinuation of beta-blockers during ADHF hospitalization (PROSPERO CRD42024557727). METHODS: We searched MEDLINE, Embase, and CENTRAL from inception to September 11, 2025. We included randomized and observational studies comparing beta-blocker discontinuation with continuation during hospitalization for ADHF and grouped studies by timing of discontinuation. We conducted meta-analysis of observational studies using generic inverse-variance random-effects models, prioritizing adjusted estimates. RESULTS: Thirteen studies met the eligibility criteria: 1 randomized trial (n = 147) and 12 cohort studies (n = 14,654). The associated risk of in-hospital mortality was uncertain for beta-blocker discontinuation vs continuation (pooled OR: 5.20; 95% CI: 0.24-113.06; I2 = 91%, 3 studies). Short-term discontinuation might be associated with higher risk of mortality up to 3 months (pooled HR: 2.30; 95% CI: 1.23-4.29; I2 = 0%, 2 studies). One study reported an adjusted estimate for long-term mortality (HR: 1.55; 95% CI: 0.69-3.51). The single randomized controlled trial showed an uncertain effect for in-hospital mortality (risk ratio: 1.77; 95% CI: 0.16-19.1) and short-term mortality (risk ratio: 0.88; 95% CI: 0.30-2.62). Findings on rehospitalization were inconsistent and did not favor either approach. All findings were low or very low certainty. CONCLUSIONS: Available evidence on beta-blocker discontinuation in ADHF is of very low certainty and findings of possible harm may reflect confounding by indication and failure to restart therapy rather than causal harm. Further high-quality randomized controlled trials and nonrandomized studies may resolve uncertainty.