Background: Ward patients who experience clinical deterioration are at high risk of mortality. Conventional rapid response systems (RRS) using track-and-trigger protocols have not consistently demonstrated improved outcomes. This study evaluated the impact of an artificial intelligence (AI)-based cardiac arrest prediction model. Methods: This 1-year, prospective, non-randomized interventional trial assigned hospitalized patients with AI-based software as a medical device (AI-SaMD) high-risk alerts to groups based on their subsequent clinical response; those reassessed or treated within 24 h comprised the AI-SaMD-guided cohort, while the remainder formed the usual care cohort. Alerts prompted an optional but not mandatory treatment review. The primary outcome was ward-based cardiac arrest; the secondary outcome was in-hospital mortality. Multivariable regression analysis was used to adjust for potential confounders. Results: Of 35,627 general ward admissions, 2906 triggered an AI-SaMD alert. Among these, 1409 (48.4%) were allocated to the AI-SaMD-guided cohort. The incidence of cardiac arrest significantly decreased from 2.07% to 1.06% (adjusted risk ratio (RR), 0.54; 95% confidence interval (CI), 0.20–0.88; p < 0.01). In-hospital mortality also significantly declined (adjusted RR, 0.65; 95% CI, 0.32–0.98; p < 0.05). Conclusions: AI-SaMD-guided alerts were associated with reductions in cardiac arrest and in-hospital mortality without requiring additional resources, supporting their integration into current clinical workflows to improve patient safety and optimize RRS performance.