(1) Background: The objectives of this study were to evaluate the concurrent and predictive validity and the applicability of the global leadership initiative on malnutrition (GLIM) criteria in patients hospitalized for acute medical conditions. (2) Methods: prospective cohort study with patients hospitalized for acute medical conditions. For validation, the methodology proposed by the GLIM group of experts was used. Sensitivity and specificity values greater than 80% with respect to those for the subjective global assessment (SGA) were necessary for concurrent validation. The time necessary to complete each nutritional assessment test was determined. (3) Results: A total of 119 patients were evaluated. The SGA was applied to the entire cohort, but the GLIM criteria could not be applied to 3.4% of the patients. The sensitivity and specificity of the GLIM criteria with respect to those for the SGA to detect malnutrition were 78.0 and 86.2%, respectively. The GLIM predictive validity criterion was fulfilled because patients with malnutrition more frequently had a hospital stay >10 days (odds ratio of 2.98 (1.21–7.60)). The GLIM criteria required significantly more time for completion than did the SGA (p = 0.006). (4) Conclusion: The results of this study do not support the use of the GLIM criteria over the SGA for the diagnosis of malnutrition in patients hospitalized for acute medical conditions.