Background: Disease-related malnutrition is a significant problem in hospitalized patients, with high prevalence rates depending on the studied population. Internal Medicine wards are the backbone of the hospital setting. However, prevalence and determinants of malnutrition in these patients remain unclear. We aimed to determine the prevalence of malnutrition in Internal Medicine wards and to identify and characterize malnourished patients. Methods: A cross-sectional observational multicentre study was performed in Internal Medicine wards of 24 Portuguese hospitals during 2017. Demographics, hospital admissions during the previous year, type of admission, primary diagnosis, Charlson comorbidity index, and education level were registered. Malnutrition at admission was assessed using Patient-Generated Subjective Global Assessment (PG-SGA). Demographic characteristics were compared between well-nourished and malnourished patients. Logistic regression analysis was used to identify determinants of malnutrition. Results: 729 participants were included (mean age 74 years, 51% male). Main reason for admission was respiratory disease (32%). Mean Charlson comorbidity index was 5.8 ± 2.8. Prevalence of malnutrition was 73% (56% moderate/suspected malnutrition and 17% severe malnutrition), and 54% had a critical need for multidisciplinary intervention (PG-SGA score ≥9). No education (odds ratio [OR] 1.88, 95% confidence interval [CI]: 1.16–3.04), hospital admissions during previous year (OR 1.53, 95%CI: 1.05–2.26), and multiple comorbidities (OR 1.22, 95%CI: 1.14–1.32) significantly increased the odds of being malnourished. Conclusions: Prevalence of malnutrition in the Internal Medicine population is very high, with the majority of patients having critical need for multidisciplinary intervention. Low education level, admissions during previous year, and multiple comorbidities increase the odds of being malnourished.