Objective: Describe the trend of the indirect standardized death rate of HIV for different modes of HIV transmission from 2003 to 2014 in Puerto Rico. Estimate the magnitude of the association between mode of HIV transmission and mortality at different time periods in Puerto Rico. Methods: ISDRs by sex and mode of transmission were computed using data from the PR National HIV/AIDS Surveillance System (2003-2014). Poisson models were used to assess the annual percent change of the ISDRs and RRs by sex. Results: Injection drug users (IDUs) showed the highest decrease in ISDR (-10.56, for men;-9.32 for women). Compared to men who have sex with men (MSM), IDU men also had the highest RR, representing an increase of 93% (2009-2011) (RRIDU vs MSM: 1.93, 95% CI: 1.66-2.23). Compared to women who were IDUs, heterosexual (HET) women had less risk of dying (48% for the period of 2006 to 2008). Conclusion: Mortality has been decreasing in each mode of transmission for both sexes. In addition, though IDUs present the highest decrease of ISDR, it is still the group whose members have the highest risk of dying, both men and women. To better describe health disparities as related to HIV/AIDS mortality, future analyses should be performed using specific causes of death and the evaluation of other relevant clinical and sociodemographic factors. Such data might increase our understanding of mortality in people with HIV/AIDS on the island, as well as help in future efforts to develop intervention strategies for the aforementioned risk groups.