Background Clinical events occurring during hospital stay are independent predictors of prolonged hospitalization, in-hospital mortality and readmission among elderly patients admitted to medical wards. Purpose To identify predictors of intercurrent clinical events (ICE) during hospital stay among the main demographic, functional and clinical characteristics assessed at hospital admission in a multicenter sample of elderly inpatients in Italy. Methods This observational prospective cohort study was conducted in 66 internal and geriatric medicine hospital wards in 2010. It enrolled 1267 inpatients aged 65 years or older living at home before hospitalization. Multivariable Poisson regression analyses were employed to identify the most common ICEs as well as their independent predictors. Results During the hospital stay 427 patients (33.7%) experienced at least one ICE. The most common ICEs were urinary tract infections, pneumonia, anemia, arrhythmias and fluid electrolyte disorders. After correction for age, sex, comorbidity, cognitive impairment and functional dependence, independent predictors of any ICE were: being a bladder catheter holder (RR [risk ratio] 1.86, 95% CI 1.52–2.27), being on treatment at home with a proton pump inhibitor (PPI) (RR 1.25, 95% CI 1.03–1.53), with immunosuppressant therapy (RR 2.10, 95% CI 1.24–3.56), and body temperature at admission (RR 1.19, 95% CI 1.06–1.33). Conclusion Four clinical characteristics, easily assessable at admission, may be useful to identify elderly inpatients at a higher risk for developing ICEs during hospital stay. Furthermore three of these predictors are modifiable factors, thus interventions reducing the use of catheter, PPI and immunosuppressants may result in reduction of ICEs.