Background In the 20th century, childhood mortality decreased rapidly, and vaccination programmes are frequently suggested as a contributing factor. However, quantification of this contribution is subject to debate or absent. We present historical data from the Netherlands that allow us to quantify the reduction in childhood mortality burden for vaccine-preventable diseases in this period as a function of vaccination coverage. Methods We retrieved cause-specific and age-specific historical mortality data from Statistics Netherlands from 1903 to 2012 (for Dutch birth cohorts born from 1903 to 1992), and data for vaccination coverage since the start of vaccination programmes from the Dutch Health Care Inspectorate and the Dutch National Institute for Public Health and the Environment. We also obtained birth and migration data from Statistics Netherlands. We used a restricted mean lifetime method to estimate cause-specific mortality burden among children and young adults for each birth cohort as the years of life lost up to age 20 years, excluding migration as a variable because this did not affect the results. To correct for long-term trends, we calculated the cause-specific contribution to the total childhood mortality burden. Findings In the prevaccination era, the contribution to mortality burden was fairly constant for diphtheria (1.4%), pertussis (3.8%), and tetanus (0.1%). Around the start of mass vaccinations, these contributions to the mortality burden decreased rapidly to near zero. We noted similar patterns for poliomyelitis, mumps, and rubella. The number of deaths due to measles around the start of vaccination in the Netherlands were too few to detect an accelerated rate of decrease after mass vaccinations were started. We estimate that mass vaccination programmes averted 148 000 years of life lost up to age 20 years (95% prediction interval 110 000-201 000) among children born before 1992. This corresponds to about 9000 deaths averted (6000-12 000). Interpretation Our historical time series analysis ...