Background: Bloodstream infections (BSIs) among people with human immunodeficiency virus (PWH) remain a poorly studied source of morbidity and mortality. We characterize the epidemiology, microbiology, and clinical outcomes including reinfection, hospitalization, and mortality rates of both community-acquired and hospital-acquired BSI in PWH. Methods: We identified all BSI, between January 1, 2000 and December 31, 2017 in PWH in care at Southern Alberta Clinic, by linking data from laboratory and clinical databases. Crude incidence rates per 1000 person-years for BSI and death were calculated. Cox proportional hazards models estimated crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) to conduct a risk factor analysis of BSI in PWH. Logistic regression models with generalized estimating equations estimated crude and adjusted odds ratios (aORs) to identify characteristics associated with 1-year mortality after BSI. Results: Among 2895 PWH, 396 BSI episodes occurred in 228 (8%) PWH. There were 278 (72%) Gram-positive and 109 (28%) Gram-negative BSI. People with human immunodeficiency virus with lower CD4 nadirs, higher Charlson comorbidity indices, and hepatitis C virus were at highest risk for BSI. Long-term all-cause mortality was greater in those experiencing BSI (HR, 5.25; 95% CI, 4.21-6.55). CD4 count <200 cells/mm3 measured closest to the time of BSI was associated with 1-year mortality after BSI (aOR, 3.88; 95% CI, 1.78-8.46). Repeat episodes (42%) and polymicrobial BSI (19%) were common. Conclusions: Bloodstream infections continue to occur at an elevated rate among PWH with high reoccurrence rates and associated morbidity and mortality. To risk stratify and develop targeted interventions, we identified PWH at greatest risk for BSI. People with human immunodeficiency virus with low immunity at the time of BSI are at highest risk of poor outcomes.