Background: Clinical trials showed mRNA-1345 (mRESVIA) was highly efficacious against RSV-associated lower respiratory tract disease in adults; real-world studies are critical to confirm vaccine impact on RSV-related healthcare usage.Methods: A retrospective matched test-negative case-control study used Veterans Health Administration electronic health records from the 2025–2026 respiratory season. Veterans aged ≥50 years with acute respiratory illness (ARI) who underwent RSV testing were included. Vaccine effectiveness (VE) of mRNA-1345 was estimated against RSV-positive ARI-associated hospitalization, urgent care/emergency department, and/or outpatient visits using multivariable conditional logistic regression. Results: The matched analysis included 2,500 RSV cases and 9,907 controls with balanced baseline characteristics. Among RSV-positive ARI-associated hospitalizations, <3 of 448 cases and 59 of 1,770 controls were vaccinated (VE of 87% (95%CI: 47%-97%)). Protection was consistent across settings.Conclusions: mRNA-1345 is associated with high protection against RSV-positive ARI-associated hospitalization that was generally consistent across medically-attended outcomes in the US Veteran population.