Introduction: Human Immunodeficiency Virus (HIV) infection is associated with acute ischemic stroke (AIS) and HIV incidence is increasing yearly. Neurological complications (NC) are common in HIV and may increase stroke risk, but no large population based studies have studied NC in HIV and the HIV-AIS association. Hypothesis: We hypothesized that: HIV prevalence among AIS is increasing over time; HIV is associated with worse outcomes and greater cost in AIS; and NC increases risk of AIS. Methods: In the Nationwide Inpatient Sample database (years 2000-2011), adult hospitalizations for AIS, HIV and NC were identified by ICD-9-CM codes; the analytic cohort constituted all AIS hospitalizations. We performed weighted analysis using chi-square, t-test, Jonckheere trend test, and the Wilcoxon rank-sum test. Results: Among 5,224,074 AIS hospitalizations, 8277(0.16%) had HIV. Those with HIV, compared to without, were more often younger (median 49 vs. 72 years; p<0.001), male (69.0% vs. 45.5%; p <0.001) and Black (59.5% vs. 15.8%; p<0.001). AIS with HIV was associated with discharge to skilled nursing facilities and intermediate care facilities (48.7% vs. 43.3%; p<0.001), lower use of Medicare/Medicaid (69.1% vs. 74.6%; p<0.001), and increased length of stay (+3 days; p<0.001) and cost (+$6714; p<0.001). Among those with HIV and AIS, only 5.6% had concurrent NC (p<0.001), including CMV encephalitis (1.45%), neurosyphilis (1.30%), cryptococcal meningitis (0.99%), cerebral toxoplasmosis (0.14%), and primary CNS lymphoma (0.13%). On trend analysis, prevalence of concurrent AIS and HIV increased from 0.11% in 2000 to 0.17% in 2011 (p<0.001). Those with HIV in AIS, compared to those without HIV, had lower prevalence of hypertension (52.6% vs. 75.6%; p<0.001) and diabetes mellitus (19.7% vs. 32.2%; p<0.001), but higher prevalence of renal disease (31.6% vs. 24.6%; p<0.001), and psychosis and depression (31.4% vs. 12.1%; p<0.001). Conclusions: There was an increasing trend over time of HIV infection in AIS hospitalizations and increased discharge to long-term care facilities and high cost burden. Further research would clarify AIS risk factors in HIV patients to mitigate adverse outcomes, considering the lower prevalence of traditional AIS risk factors.