OBJECTIVE: Ongoing HIV replication while receiving combination antiretroviral therapy (cART) may reduce survival. Viremia copy-years (VCY) has shown improved mortality risk prediction over single time-point viral load (VL) measures. However, the timing of a patient's VL history most associated with later mortality has not been studied. Here we determined the optimal duration and temporality of VL history for predicting mortality. DESIGN: Survival analysis among HIV-positive men who initiated cART in the Multicenter AIDS Cohort Study (1995-2015). METHODS: VCY measures were derived from area-under-the-VL-curve. The overall VCY based upon the complete post-cART VL history was compared to 20 VCYs derived from VLs assessed during different shorter time periods (the most recent 1-10 years and initial 1-10 years following cART initiation) for associations with mortality. RESULTS: Each 10-fold increase in VCYs based on the most recent 3-8 years was significantly associated with 23-26% decrease in survival times, a magnitude of effect greater than that of the most recent VL (16%). These associations were independent of CD4 cell count and single time-point VLs. In addition, the degree of pre-cART immunodeficiency did not affect the mortality prognostic value of VCY based on VLs in the most recent 3 years. Conversely, the overall VCY and VCYs based on VLs immediately following cART initiation were not independent predictors of mortality. CONCLUSION: Among cART-treated men, VCY based upon VLs in the recent 3 years (6 VLs), has a mortality prognostic value greater than that of the overall VCY and single time-point VLs, making the former a more feasible measure for use.