The article deals with one of the major medical demographic problems of Tver region's higher population mortality, including mortality of able-bodied population. The prevalence of main causes of death and their structure are analyzed. The prospective forecast of death rate indicators based on extrapolation technique is proposed. The main strategic approaches to the development of target programs of decreasing premature population mortality in Tverskaya oblast on the basis of the expertise of hospital lethality and analysis of demographic situation is presented. The proposed approaches can promote the study of optimal management and organization decision-making by administrations of different levels.