Quantitative knowledge of the turnover of different leukocyte populations is key to our understanding of immune function in health and disease. A lot of progress has been made thanks to the introduction of stable isotope labeling, the state of the art technique for in vivo quantification of cellular life spans. Yet, even leukocyte life span estimates based on stable isotope labeling can vary up to ten-fold between laboratories. We investigated whether these differences could be due to differences in the length of the labeling period between studies. To this end, we performed deuterated water labeling experiments in mice, in which only the length of label administration was varied. The resulting life span estimates were indeed dependent on the length of the labeling period when the data were analyzed using a commonly used single-exponential model. We show that multi-exponential models provide the necessary tool to obtain life span estimates that are independent of the length of the labeling period. Use of a multi-exponential model enabled us to reduce the gap between human T-cell life span estimates from two previously published labeling studies. This provides an important step toward unambiguous understanding of leukocyte turnover in health and disease.