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This study was performed to evaluate the measurement properties of Youth Quality of Life–Short Form (YQOL-SF) in assessing the quality of life (QOL) among general youths in Vietnam. An online cross-sectional study was conducted to validate the YQOL-SF. Factor analysis (including exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) was utilized to determine the factorial structure of this tool. The psychometric properties (reliability and validity) of the new factorial model were assessed. The factor analysis revealed the two-factor model of YQOL-SF including factor 1 “Belief in self and family”, and factor 2 “Environment and relationships”. Cronbach’s alpha value showed excellent internal consistency in both factors (0.911 and 0.910, respectively). Results also indicated good convergent, divergent, concurrent, and know-group validity of the two-factor model. Our study provided a promising model with different domains that were proved to be essential for the assessment of quality of life among Vietnamese youth aged 16–24. Our two-factor model affirmed that a balance between detail and length of the assessment is important to consider when selecting YQOL-SF for youths’ QOL assessment. It helped reduce the risk of redundancy and encourages high survey completion rates among participants.