Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in the Western countries, however, it is infrequent in the Eastern countries. The direct antiglobulin test (DAT) may be positive at some time during the disease course of CLL. The aim of this study was to explore the prognostic impact of positive DAT at diagnosis in Chinese patients with CLL. In 123 Chinese patients with CLL, 34 (27.6%) patients presented with a positive DAT at diagnosis. However only 12 patients (9.8%) with a positive DAT developed autoimmune hemolytic anemia (AHA). According to the correlation analysis, advanced Binet stage (p < 0.001), high level of serum lactate dehydrogenase (LDH) (p = 0.003) and beta(2)-microglobulin (beta(2)-M) (p = 0.011), unmutated immunoglobulin heavy chain variable gene status (p < 0.001), positive ZAP-70 (p = 0.012), and trisomy 12 cytogenetic aberration (p = 0.004) emerged as factors significantly related to the occurrence of DAT-positive. Patients with positive DAT had significantly shorter survival times than patients with negative DAT (p = 0.009). Five-year OS percentages of DAT-positivity and DAT-negative patients were 72.8% and 97.5%, respectively. It was showed that DAT status might be applied for the assessment of prognosis in patients with CLL.