Abstract Purpose: Beta blockers (BBs) have long been used for the treatment of cardiovascular and other medical conditions. More recently, the role of beta-adrenergic signaling in multiple processes driving tumor progression has been highlighted by preclinical studies, generating growing clinical interest in the potential repurposing of BBs as adjunctive anticancer agents. However, observational studies thus far have yielded mixed conclusions regarding their potential clinical use in oncology, and positive results may be inflated due to time bias (ITB). The main objective of this meta-analysis was to better characterize the association between beta blockade and survival in cancer patients, considering possible biases. Methods: OVID Medline, EMBASE, and CENTRAL were searched from database inception to September 13, 2023 for research publications comparing the survival of cancer patients using BBs to that of non-users. In the large majority of studies, BBs were used to treat relevant patient cardiac comorbidities, not as adjunctive anti-cancer agents. Data extraction and quality assessments, using ROBINS-I, were conducted in duplicate. Hazard ratios (HRs) were analyzed using a random-effects model, with heterogeneity measured by the I2 statistic. Exploratory subgroup analyses assessed the association of BB type (selective vs. non-selective), cancer stage (early vs. advanced), and cancer type with survival. Sensitivity analysis was performed to assess the influence of ITB. The systematic review was prospectively registered (PROSPERO CRD42020200238) and not funded. Results: We identified 79 eligible studies comprising 213 distinct analyses and 492,381 total patients. 2/79 studies were prospective (2.5%), while the remainder were retrospective. The most common primary tumor types assessed included breast (n=33), ovarian (n=30), and colorectal (n=28). Advanced disease (n=56) was more commonly studied than early/non-metastatic disease (n=26). Beta-blocker use was associated with significantly longer progression-free survival (PFS) than non-use, with a pooled HR of 0.78 ([95% CI: 0.66-0.92], I2=79.8%). This remained significant after excluding studies at greater risk of ITB (HR 0.74 [95% CI: 0.61-0.91], I2=36.6%). HRs for cancer-specific survival (CSS) and overall survival (OS) were 0.95 ([95% CI: 0.91-1.00], I2 = 77.4%) and 0.99 ([95% CI: 0.94-1.04], I2 = 84.9%). Conclusion: This meta-analysis found that beta blockade may be associated with longer PFS among patients with cancer, irrespective of cancer type or stage; these findings remained statistically significant after excluding studies at risk of ITB. There was also a trend for BB use and longer CCS, but no difference observed for OS in the overall cohort. This lack of detriment to OS in the included observational studies is notable given that BBs are most commonly prescribed to patients with cardiovascular disease who are likely at inherently higher risk of death than non-user counterparts due to cardiac comorbidities. Ultimately, conclusions of this meta-analysis are limited by the observational nature of eligible studies. However, multiple phase II trials are ongoing, including a recently registered trial (NCT05741164) seeking to determine the efficacy of propranolol in combination with pembrolizumab in patients with checkpoint inhibitor refractory metastatic triple-negative breast cancer. If positive, findings of these trials will lay the foundation for future larger randomized controlled trials to establish the highest level of evidence in this field. Citation Format: Stephanie Chan, Adam Komorowski, Xingshan Cao, Yizhuo Gao, Kushal Kshatri, Kairavi Desai, Markus Kuksis, Michael Rosen, Anjali Sachdeva, Isabella Kojundzic, Saif Samari, Iacovos Michael, Husam Abdel-Qadir, Katarzyna J Jerzak. The Impact of Beta Blocker Use on the Survival of Cancer Patients: A Systematic Review and Meta-Analysis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-12-30.