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• Secondary infections prevail in North Vietnamese adults with few cases of severe disease. • Dengue virus serotypes DENV1 and DENV2 are predominant with higher viremia in primary infection than secondary infection. • Adult secondary dengue infection is distinguished by IgM:IgG ratio cut off <0.7. • Platelet loss correlates with dengue-specific IgG and IgM levels but does not necessarily lead to longer hospital stay or worsening illness. • Platelet autoantibodies in acute dengue infection and autoimmune complications in post-dengue warrant further investigation. The morbidity in dengue fever is dependent on the dengue virus (DENV) serotypes, the patient age, predisposing immunogenic markers and the frequency of primary and secondary infections. This study aims to distinguish acute primary from secondary dengue infections of Vietnamese adults and to assess the association of viremia and anti-dengue immunoglobulin levels with clinical outcomes. Viral RNA, dengue serotypes and levels of anti-dengue IgM and IgG of hospitalized adult cases were determined in EDTA-plasma samples prospectively collected during three consecutive years of dengue infection in Hanoi. Patients admitted to hospital within 7 days of their 1st reported fever were included. Primary infections were anti-dengue IgG enzyme-linked immunosorbent assay (ELISA) negative on both day of hospital entry (day 0) and day two or three of hospitalization (day 2 or 3) with a positive anti-dengue IgM on either day 0 or day 2 or 3 hospitalization. The secondary infections were anti-dengue IgG ELISA positive on both day 0 and day 2 or 3 with positive anti-dengue IgM ELISA on either day 0 or day 2 or 3. The hospitalized dengue fever cases between October 2016 and March 2019 were predominantly secondary infections (74%, 68% and 77%, respectively) with DENV-1 (60% and 65%) and DENV-2 (22% and 26%) serotypes determined in the latter two years. The viremia in primary infection was significantly higher than that in secondary infection (P < 0.01) and positively correlated with the days of hospital stay. In secondary infections, platelet counts were lower than in primary infections (P = 0.04) and IgG levels in secondary infection negatively correlated with platelet counts (Spearman's r = −0.22, P < 0.01). Our results indicate high rates of secondary infection with DENV1 and DENV2 serotypes. Anti-dengue immunoglobulins negatively correlate with hospital stay and platelet counts with few warning signs or severe disease. Further investigations of specific antibodies in adults which predict auto-inflammatory activity after the recovery from dengue infection are warranted. [ABSTRACT FROM AUTHOR]