OBJECTIVES:  To describe a functional approach of a population database for monitoring health economics, patient’s outcomes and impact of new drugs. The need to use real-world data to support clinical research was the main driver for the Italian Inter-university Consortium (CINECA) to set-up a population-based patient centric database (ARNO Observatory). METHODS: The Italian National Health Service (NHS) is a Public Health System, providing healthcare assistance to all the population. Since 1987, ARNO Observatory collects and integrates administrative and clinical data for each single patient with high quality and complete information of patient demographics, NHS reimbursed drugs dispensed, hospital discharges, lab tests prescriptions.  RESULTS: ARNO, with its patient centric approach, provides comprehensive data from a population of over 11 million of patients of a network of 32 Italian Local Health Units. Integration of administrative and clinical data is important to study patient care pathways,  to evaluate appropriateness of medical prescriptions, to evaluate real world outcome and to reduce health expenditure.  This patient centric approach led to the creation of disease-specific observatories such as diabetes, cardiovascular disease, osteoporosis, etc…, with access to data tailored on specific user profiles at national or local level. The aim is to examine the safety and/or effectiveness of healthcare products and services in the real-world by measuring performance indicators and impact of new drugs. CONCLUSIONS: ARNO Observatory is an important source of information able to show both economical indicators and the good practice of treatment. In particular ARNO enables Health Units and Professionals to conduct research projects on disease management, and benchmarking and it is a valid instrument for epidemiological and economic planning for decision making in Italy.