BACKGROUND: Mortality statistics are traditionally used to quantify the burden of disease and to determine the relative importance of the various causes of death. Some of the most frequently used indices to quantify the burden of disease are the years of potential life lost (YPLL) and years of potential productive life lost (YPPLL). These two measures reflect the mortality trends in younger age groups and they provide a more accurate picture of premature mortality. This study was carried out to determine YPLL, YPPLL and cost of productivity lost (CPL) due to premature mortality caused by selected causes of deaths in Tanzania. METHODS AND FINDINGS: Malaria, respiratory diseases, HIV/AIDS, tuberculosis, cancers and injuries were selected for this analysis. The number of deaths by sex and age groups were obtained from hospital death registers and ICD-10 reporting forms in 39 public hospitals in Tanzania, covering a period of 2006-2015. The life expectancy method and human capital approach were used to estimate the YPLL, YPPLL and CPL due to premature mortality. During 2006-2015, malaria, HIV/AIDS, tuberculosis, respiratory diseases, HIV+tuberculosis, cancer and injury were responsible for a total of 96,834 hospital deaths, of which 46.4% (n = 57,508) were among individuals in the productive age groups (15-64 years). The reported deaths contributed to 2,850,928 YPLL (female = 1,326,724; male = 1,524,205) with an average of 29 years per death. The average YPLL among females (32) was higher than among males (28). Malaria (YPLL = 38 per death) accounted for over one-third (35%) of the total YPLL. There was a significant increase in YPLL due to the selected underlying causes of death over the 10-year period. Deaths from the selected causes resulted into 1,207,499 YPPLL (average = 21 per death). Overall, HIV/AIDS contributed to the highest YPPLL (323,704), followed by malaria (243,490) and injuries (196,505). While there was a general decrease in YPPLL due to malaria, there was an increase of YPPLL due to HIV/AIDS, respiratory diseases, cancer and injuries during the 10-year period. The total CPL due to the six diseases was US$ 148,430,009 for 10 years. The overall CPL was higher among males than females by 29.1%. Over half (58%) of the losses were due to deaths among males. HIV/AIDS accounted for the largest (29.2%) CPL followed by malaria (17.8%) and respiratory diseases (14.6%). The CPL increased from US$11.4 million in 2006 to US$17.9 million in 2016. CONCLUSIONS: The YPLL, YPPLL and CPL due to premature death associated with the six diseases in Tanzania are substantially high. While malaria accounted for highest YPLL, HIV/AIDS accounted for highest YPPLL and CPL. The overall CPL was higher among males than among females. Setting resource allocation priorities to malaria, HIV/AIDS and respiratory diseases that are responsible for the majority of premature deaths could potentially reduce the costs of productivity loss in Tanzania.