The leading causes of death in the Umbria Region (Italy) between 1994-2008 were analysed and a comparison was made between data from three five-year time periods: 1994-1998, 1999-2003 and 2004-2008. Standardized rates of Years of Potential Life Lost (YPLL) at 75 years, by gender and cause of death, were also measured. Mortality data was obtained from the Umbria Registry of causes of death; diagnoses were codified according to the International Classification of Diseases 10th revision (ICD10). Mortality trends over time were analysed by using standardized mortality rates with the 2001 Umbria census data as the reference population . The joinpoint regression program was used to analyze rates calculated by the SEER (Surveillance Epidemiology and End Results) software of the National Cancer Institute (USA). Mortality for all causes, standardised by age, show a significantly decreasing trend from 1994 to 2008 in both genders. Mortality rates for cardiovascular diseases and malignant tumours show a significant constant decline in both genders. Standardised rates of YPLL at 75 years declined by 32% in males and 29% in females between the five-year period 1994-1998 and the period 2004-2008. In conclusion, a generalised decline in mortality and a shift towards older age groups is observed with a consequent decline in YPLL, allowing a positive judgment to be given regarding the efficacy of preventive, therapeutic and rehabilitation interventions implemented by the regional health care system.