OBJECTIVES: Polypharmacy has been associated with functional decline and adverse outcomes in vulnerable population and with an increased risk of Adverse Drug Events (ADE), particularly in fragile patients such as the elderly with complex medical conditions.Aim of this observational study was to describe and evaluate ADE in patients with polypharmacy by a digital health service that prevents Drug-Drug Interactions (DDI) using the social security number (SSN). METHODS: A cohort of 369 patients was identified through a closed loop, fully automated system that records and updates all the drugs taken during therapy cycle/s by specifically designed software interfaces loaded on Information and Communication Technology programs of the network.The tool was designed to support General Physicians in clinical decisions, providing them information about prescribed drugs/over the counter (OTC)/herbs, detailing dosage, comorbidity, number of packages and pills per package,  prescription/purchase date. RESULTS: About 30% of patients shown 1 comorbidity and 11.8% 2 or more. Cardiovascular diseases (22.7%) represented the most frequent comorbidity, followed by musculoskeletal pathology (13.6%), diabetes (8.6%), cancer (5.1%), and depression (4.8%).The Charlson Comorbidity Index was 0 in 65.2%, 1 in 25.7%, 2 in 7.0% and 3 to 4 in 2.1%. A total of 67 patients (mean age 72 years; 52.2% women) had at least 1 DDI. About 50% (N = 33) had up to 2 DDIs,            25% from 3 to 7 DDIs and 25% ≥8 (from 9–74 DDIs per person). A total of 501 DDIs were identified: the severity was low in 35.5%, moderate in 59.7% and high in 4.8%. The top 10 drugs involved in DDI were: acetylsalicylic acid (ASA), hydrochlorothiazide, ibuprofen, diclofenac, digoxin, nebivolol, pantoprazole, ramipril, furosemide and nimesulide. CONCLUSIONS: ICT technologies are useful to timely identify DDIs of clinical relevance and the drugs most frequently involved.