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Background. The wide distribution and high case-fatality ratio of severe fever with thrombocytopenia syndrome (SFTS) have made it a significant public health problem. This study was designed to identify the predictors of fatal outcomes and to evaluate the effectiveness of antiviral therapy in treating SFTS virus (SFTSV)–infected patients. Methods. A cross-sectional study was performed in a general hospital located in Xinyang city, whereas the largest number of patients with SFTS in China were treated during 2011–2012. The primary outcome for the treatment effect analysis was death. Other outcomes included sequential platelet levels and viral loads observed throughout the hospitalization and the interval between the initiation of ribavirin therapy and the return of the platelet count to a normal level. Results. A total of 311 SFTSV-infected patients were included in the study. The most frequent clinical presentations were fever, weakness, myalgia, and gastrointestinal symptoms. Each patient had thrombocytopenia, leukopenia, or both. The case-fatality ratio (CFR) was 17.4% (95% confidence interval [CI], 13.1%–21.6%). Older age (odds ratio [OR], 1.061; 95% CI, 1.023–1.099; P = .001), decreased level of consciousness (OR, 5.397; 95% CI, 2.660–10.948; P < .001), and elevated levels of lactate dehydrogenase (>1200 U/L; OR, 2.620; 95% CI, 1.073–6.399; P = .035) and creatine kinase (>800 U/L; OR, 2.328; 95% CI, 1.129–4.800; P = .022) were significantly associated with fatal outcome. The CFRs were similar between patients who received ribavirin and those who did not. Ribavirin treatment showed no significant effect on either platelet counts or viral loads during hospitalization of patients with fatal or nonfatal cases. Conclusions. These findings can improve knowledge about the characteristics of patients with fatal outcomes and the use of antiviral drug for SFTS.