Background: Frailty and sarcopenia are associated with frequent hospitalizations and poor clinical outcomes in geriatric patients. Ascertaining this association for younger patients hospitalized in internal medicine departments could help better prognosticate patients in the realm of internal medicine. Methods: During a 1-year prospective study in an internal medicine department, we evaluated patients upon admission for sarcopenia and frailty. We used the FRAIL questionnaire, blood alanine-amino transferase (ALT) activity, and mid-arm muscle circumference (MAMC) measurements. Results: We recruited 980 consecutive patients upon hospital admission (median age 72 years (IQR 65–79); 56.8% males). According to the FRAIL questionnaire, 106 (10.8%) patients were robust, 368 (37.5%) pre-frail, and 506 (51.7%) were frail. The median ALT value was 19IU/L (IQR 14–28). The median MAMC value was 27.8 (IQR 25.7–30.2). Patients with low ALT activity level (<17IU/L) were frailer according to their FRAIL score (3 (IQR 2–4) vs. 2 (IQR 1–3); p < 0.001). Higher MAMC values were associated with higher ALT activity, both representing robustness. The rate of 30 days readmission in the whole cohort was 17.4%. Frail patients, according to the FRAIL score (FS), had a higher risk for 30 days readmission (for FS > 2, HR = 1.99; 95CI = 1.29–3.08; p = 0.002). Frail patients, according to low ALT activity, also had a significantly higher risk for 30 days readmission (HR = 2.22; 95CI = 1.26–3.91; p = 0.006). After excluding patients whose length of stay (LOS) was ≥10 days, 252 (27.5%) stayed in-hospital for 4 days or longer. Frail patients according to FS had a higher risk for LOS ≥4 days (for FS > 2, HR = 1.87; 95CI = 1.39–2.52; p < 0.001). Frail patients, according to low ALT activity, were also at higher risk for LOS ≥4 days (HR = 1.87; 95CI = 1.39–2.52; p < 0.001). MAMC values were not correlated with patients’ LOS or risk for re-admission. Conclusion: Frailty and sarcopenia upon admission to internal medicine departments are associated with longer hospitalization and increased risk for re-admission.