Chronic infections are a major factor in the development of pulmonary embolism (PE). We aimed to evaluate the trends of PE-related hospitalizations and PE-related deaths in people living with HIV (PLWH) during the era of combination antiretroviral therapy (cART) through a retrospective study in Spain. Data were collected from the Minimum Basic Data Set (MBDS) between 1997 and 2013. The study period was fragmented into four calendar periods (1997-1999, 2000-2003, 2004-2007, and 2008-2013). The rate of PE-related hospitalizations remained stable in PLWH (P = 0.361). HIV-monoinfected patients had a higher incidence than HIV/HCV-coinfected patients during all follow-up [(98.7 (95%CI = 92.2; 105.1); P < 0.001], but PE incidence decreased in HIV-monoinfected patients (P < 0.001) and increased in HIV/HCV-coinfected patients (P < 0.001). Concretely, the rate of PE-related hospitalizations decreased significantly in patients monoinfected with HIV [from 203.6 (95%CI = 175.7; 231.6) events per 100,000 patient-years in 1997-1999 to 74.3 (95%CI = 66.1; 82.3) in 2008-2013; P < 0.001], while patients coinfected with HIV/HCV had a significant increase [from 16.3 (95%CI = 11; 21.6) in 1997-1999 to 53.3 (95%CI = 45.9; 60.6) in 2008-2013; P < 0.001]. The mortality rate of PE-related hospitalizations showed a similar trend as PE incidence. In conclusion, the epidemiological trends of PE in PLWH changed during the cART era, with decreases in incidence and mortality in HIV-monoinfected and increases in both variables in patients coinfected with HIV/HCV.