Background/Objectives: Two-dimensional echocardiography (2D echo) is widely used for assessing left ventricular ejection fraction (LVEF). This single-center comparative study aims to evaluate the accuracy of LVEF measurements obtained using the AI-assisted handheld ultrasound device Kosmos against cardiac magnetic resonance (CMR), the current gold standard. Methods: A total of 49 adult patients undergoing clinically indicated CMR were prospectively enrolled. AI-based LVEF measurements were compared with CMR using the Wilcoxon signed-rank test, Pearson correlation, multivariable linear regression, and Bland–Altman analysis. All analyses were performed using STATA v18.0. Results: Median LVEF was 57% (CMR) vs. 55% (AI-Echo), with no significant difference (p = 0.51). Strong correlation (r = 0.99) and minimal bias (1.1%) were observed. Conclusions: The Kosmos AI-based autoEF algorithm demonstrated excellent agreement with CMR-derived LVEF values. Its speed and automation make it promising for bedside assessment in emergency departments, intensive care units, and outpatient clinics. This study aims to fill the gap in current clinical evidence by evaluating, for the first time, the agreement between LVEF measurements obtained via Kosmos’ AI-assisted autoEF and those from cardiac MRI (CMR), the gold standard for ventricular function assessment. This comparison is critical for validating the reliability of portable AI-driven echocardiographic tools in real-world clinical practice. However, these findings derive from a selected population at a single Italian center and should be validated in larger, diverse cohorts before assuming global generalizability.