Malnutrition–sarcopenia syndrome (MSS) is frequent in the hospital setting. However, data on the predictive validity of sarcopenia and MSS are scarce. We evaluated the association between sarcopenia and MSS and clinical adverse outcomes (prolonged length of hospital stay—LOS, six-month readmission, and death) using a prospective cohort study involving adult hospitalized patients (n = 550, 55.3 ± 14.9 years, 53.1% males). Sarcopenia was diagnosed according to the EWGSOP2, and malnutrition according to the Subjective Global Assessment (SGA). Around 34% were malnourished, 7% probable sarcopenic, 15% sarcopenic, and 2.5% severe sarcopenic. In-hospital death occurred in 12 patients, and the median LOS was 10.0 days. Within six months from discharge, 7.9% of patients died, and 33.8% were readmitted to the hospital. Probable sarcopenia/sarcopenia had increased 3.95 times (95% CI 1.11–13.91) the risk of in-hospital death and in 3.25 times (95% CI 1.56–6.62) the chance of mortality in six months. MSS had increased the odds of prolonged LOS (OR = 2.73; 95% CI 1.42–5.25), readmission (OR = 7.64; 95% CI 3.06–19.06), and death (OR = 1.15; 95% CI 1.08–1.21) within six months after discharge. Sarcopenia and MSS were predictors of worse clinical outcomes in hospitalized patients.