Objective:To compare the clinical features between chronic active Epstein-Barr virus infection(CAEBV) and infectious mononucleosis(IM)in adult patients.Methods:Clinical data from 56 adult IM patients and 14 adult CAEBV patients admitted in the First Affiliated Hospital of Nanjing Medical University during January 2011 to December 2019 were enrolled. Clinical manifestations, laboratory indicators, treatment and outcomes were compared between two groups. Chi-square test and Mann-whitney U test were used to analyze data. Results:The average age of CAEBV patients was higher than that of IM patients [36.0(23.8, 50.5)years vs. 19.0(17.3, 22.8) years; U=90.0, P<0.05]. The symptoms of sore throat, throat congestion, tonsilla enlargement and lymphadenopathy in IM group were more common than those in CAEBV group( χ2=14.088, 16.875, 31.855 and 10.938, all P<0.01). However, the incidence of pulmonary infection, sleepiness/dysphoria and splenomegaly in CAEBV group were significantly higher than those in IM group( χ2=17.217, 5.809 and 6.254, P<0.05 or <0.01). The white blood cell counts, hemoglobin levels, platelet counts, alanine aminotransferase(ALT) and albumin in CAEBV group were significantly lower than those in IM group( U=47.0, 49.5, 158.5, 173.0 and 263.5, all P<0.01). The levels of neutrophil ratio, C-reactive protein, serum ferritin and EBV DNA load in CAEBV group were significantly higher than those in IM group( U=145.0, 140.0, 128.5 and 115.0, P<0.05 or <0.01). The proportions of CD3 + T cell counts and CD8 + T cell counts in CAEBV group were significantly lower compared to those in IM group( U=42.0 and 24.5, P<0.01); the proportions of CD4 + T cell counts, the CD4 + T/CD8 + T cell counts ratio and B lymphocytes in CAEBV group were significantly higher compared to those in IM group( U=29.0, 23.5 and 34.5, P<0.01). Fifty-six IM patients were all cured and discharged from hospital. In CAEBV group, 8 cases died, 3 cases were improved and 3 cases lost follow-up. Conclusions:Patients with IM represent a favorable prognosis, while the prognosis of CAEBV is relatively poor and complication with HLH may occur. For older patients with EBV infection complicated with pulmonary infection, lethargy/irritability, attention should be paid to monitor blood routine, liver function, serum EBV DNA load and peripheral blood lymphocyte subsets.