Diagnosing dengue in febrile patients is challenging. Of a total of 459 patients with acute undifferentiated fever, randomly selected from 12 primary health facilities and 1 clinic of the provincial malaria station in southern Vietnam, dengue-specific antibody (Ab) and NS1Ag enzyme-linked immunosorbent assay (ELISA) (Platelia, Bio-Rad Laboratories, Hercules, CA 94547, US) were performed on acute (t0) and convalescent (t3 weeks) sera. Polymerase chain reaction (PCR) was used for confirmation. Based on a composite of the NS1Ag-ELISA, Ab-ELISA, and PCR results, 54 (12%) patients had acute dengue. Positive and negative predictive values were 65% and 98% for the Ab-based diagnosis and 91% and 92% for NS1Ag, respectively. The agreement between Ab- and NS1Ag-based diagnosis was poor (kappa value, 0.2). Two patients without dengue had detectable NS1Ag on t0 and t3, 1 just above the cutoff value and 1 with very high values. For 5 dengue patients, NS1Ag was still detectable at very high levels at t3. Dengue NS1Ag can be used for early diagnosis of dengue; infrequent false-positive results need further clarification.