The aim of this study was to evaluate trends of potential years of life lost (PYLL) rates in the Slovak population and analyze the average annual percent change (AAPC) of PYLL rates regarding the most common causes of death between 2004 and 2013. National mortality and demographic data were obtained from the Statistical Office of the Slovak Republic, and 378,535 causes of death within the period were analyzed. The PYLL values in both genders and each disease category were added up across all age groups to form annual values. For the trend analysis, the AAPC indicator was proposed. The PYLL rate is age-standardized and expressed as a sum of all deaths per 100,000. In the period 2004-2013, the highest mean PYLL rates were observed in neoplasms in the whole population (2,103 per 100,000), as well as in females (2,088 per 100,000), with a permanent high significant increase of AAPC of PYLL in both genders. The second highest mean PYLL rate in the ten-year period was related to circulatory system diseases in total (1,922 per 100,000) as well as in females (1,449 per 100,000). In males, circulatory system diseases had the highest PYLL rate (2,397 per 100,000). The PYLL rates trend regarding external causes of morbidity and mortality showed the most notable decrease in the assessed period and the AAPC of PYLL showed significant negative values both in males (-2.5%; p < 0.001) and females (-4%; p < 0.001). Our results should contribute in developing intervention programs aimed at reducing the burden of premature mortality since the main causes of premature death are associated to well-known and preventable risk factors.