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Background. Toxoplasmosis-related hospitalizations often occur in persons with human immunodeficiency virus (HIV) infection and other causes of immunosuppression.Methods. Using the National Inpatient Sample (NIS) from the Healthcare Cost and Utilization Project, we examined trends in toxoplasmosis-related hospitalizations by HIV infection status from 1993 through 2008, and rates by sex and race or ethnicity in 2008. The NIS is designed to represent a 20% sample of US community hospitals and currently includes information on up to 8 million discharges per year from ∼1000 hospitals. We used International Classification of Diseases, Ninth Revision, Clinical Modification codes 130–130.9 for toxoplasmosis and 042-044/795.8/795.71/V08 for HIV infection.Results. Estimated HIV-associated toxoplasmosis hospitalizations increased from 9395 in 1993 to 10583 in 1995 (P = .0002), then dropped to 3643 in 2001 (P < .0001), with similar levels thereafter. The rate of HIV-associated toxoplasmosis hospitalizations among all HIV-related hospitalizations decreased from 3.33% in 1993 to 1.25% in 2008 (P < .0001). Estimated non–HIV-associated toxoplasmosis hospitalizations were less variable from 1993 to 2008 (range, 386–819; 0.0020% in 1993, 0.0015% in 2008). In 2008, the rates of both HIV- and non–HIV-associated toxoplasmosis hospitalizations were higher in Hispanic persons than in white persons.Conclusions. HIV-associated toxoplasmosis hospitalizations dropped markedly after 1995 when highly active antiretroviral therapy was introduced; however, hospitalizations decreased relatively little after 2000, suggesting late diagnosis of some HIV-infected persons or antiretroviral therapy failure. Non–HIV-associated toxoplasmosis hospitalizations have been more stable. The rates of toxoplasmosis-related hospitalizations varied markedly among racial and ethnic groups.