A clinical trial comparing shortened tuberculosis prevention protocols found that one-month daily rifapentine plus isoniazid produced comparable adverse event rates to the standard three-month weekly rifapentine-isoniazid regimen. The study tracked safety outcomes across both treatment arms, measuring hepatotoxicity, drug discontinuation rates, and serious adverse events in participants at high TB risk. This finding addresses a critical barrier to TB prevention compliance, as shorter treatment durations historically improve patient adherence rates. The one-month protocol could significantly expand preventive therapy uptake in high-burden settings where treatment completion remains challenging. Current WHO guidelines recommend 3-6 month prevention courses, but poor adherence limits real-world effectiveness. The comparable safety profile of the ultra-short regimen suggests it could become the preferred approach for latent TB treatment, particularly in resource-limited settings where follow-up is difficult. However, the study focused primarily on safety rather than efficacy endpoints, and broader implementation will require demonstration of non-inferior protection against active TB development. If efficacy matches safety, this compressed timeline could transform global TB prevention strategies by removing adherence barriers that currently undermine prevention programs.