We translated the Effort-Reward imbalance questionnaire, an instrument for measuring work stress, into the Vietnamese language and investigated its psychometric properties among nurses in Vietnam. In a hospital-based cross-sectional study design, we sampled and interviewed 207 nurses working full-time (response rate 83%). We evaluated the internal consistency using standardized Cronbach's alpha coefficients and structural validity using confirmatory factor analysis. Discriminative validity was assessed by comparing the measured scores between age groups, gender, education levels, income groups, and job positions. In addition, we confirmed the criterion validity by investigating its association with self-reported health using simple and multiple logistic regression models. Most of the participants were female (73.3%), young (average 28.5 years old), and had education levels of college or higher (53.5%). We observed sufficient internal consistency in effort, reward, and over-commitment scales (Cronbach's alpha 0.80, 0.76, and 0.68, respectively). Confirmatory factor analysis of the three-factor hierarchical model showed an acceptable fit and fair construct validity with most moderate or stronger (>0.3) factor loading coefficients. Poor self-rated health was more likely in respondents in both Effort-Reward ratio's middle tertile (adjusted Odd-Ratio = 2.80, p-value = 0.031) and highest tertile (adjusted Odd-Ratio = 2.64, p-value = 0.05), adjusting for age, gender, and education levels. The Effort-reward imbalance scale has adequate reliability and validity for assessing work stress among nurses in Vietnam. Its significant association with poor self-rated health warrants further investigation. The validated instrument can help measure the effort-reward imbalance to manage better work-related emotional strains and mental health issues among nurses and ensure human resources' stability in healthcare in Vietnam.