Background <p>Hand hygiene is critical for infection prevention and quality of care. Alcohol-based hand rubs (ABHRs) are widely recommended for their broad antimicrobial activity and ease of use; however, concerns remain regarding product quality and efficacy. This study evaluated the physicochemical properties and antimicrobial performance of ABHRs used in healthcare facilities in Addis Ababa.</p> Methods <p>A laboratory-based experimental design was conducted between May and August 2025. Thirty ABHRs from hospital-produced, locally manufactured, and imported sources were tested using a customized EN 1500 protocol. The volunteers’ hands were contaminated with <i>Escherichia coli</i> K12 and treated with 3 mL of the product for 30&#xa0;s. Pre- and post-treatment bacterial counts were compared, with log₁₀ reduction factor as the primary outcome. Non-parametric tests (Wilcoxon signed-rank, Kruskal–Wallis, and Mann–Whitney U) were applied.</p> Results <p>Measured ethanol concentrations ranged from 55 to 86% v/v compared with labeled 60–87% v/v. Nearly one-quarter of hospital-produced and locally manufactured products fell below the WHO minimum of 60% v/v. Antimicrobial testing showed log₁₀ reductions of 2.63–4.63; 50% achieved the EN 1500 benchmark of ≥ 4 log reduction, 26.7% demonstrated moderate efficacy (3–&lt;4 log reduction), and 23.3% fell below 3 log reduction. Imported formulations (73–86% v/v; median 79% v/v) consistently achieved ≥ 4 log reductions, significantly outperforming hospital-produced (<i>p</i> = 0.009) and locally manufactured products (<i>p</i> = 0.047).</p> Conclusion <p>One-fourth of ABHRs and half of the tested products failed to meet the WHO concentration and EN 1500 efficacy benchmarks. Policymakers, hospital administrators, and the Ethiopian Food and Drug Authority must urgently establish mandatory quality audit systems and enforce strict adherence to international guidelines to safeguard healthcare workers, patients, and infection prevention efforts in Ethiopia.</p>