A retrospective cohort study was conducted using production and health records from Québec dairy herds which were integrated with the objectives of calculating different lifetime profitability measures and developing analyses of the impact of selected reproduction and health variables on profitability. The dataset for the study consisted of lifetime records for a total of 13 668 Holstein cows from 113 herds and in cohorts of cows calving for the first time between 2000 and 2009. To calculate profit, all the revenues and costs were accumulated on a lifetime basis, and cumulative lifetime profit and cumulative lifetime profit adjusted for the opportunity cost of postponed replacement were selected for analysis. There were statistically significant effects in both profit measures because of age at first calving, cumulative number of days in milk, and cumulative number of days dry as well as the number of health events accumulated by animal lifetime (clinical mastitis, reproductive problems, and feet and legs problems). The results of lifetime profit measures and management variables with an effect on profit results could help dairy producers in the process of monitoring and making decisions regarding profit goals and herd life of their cows.