The main objective of this study was to use the translated version of Hospital Survey on Patient Safety Culture, the English-Vietnamese Hospital Survey on Patient Safety Culture (E-V HSOPSC), to assess the patient safety culture in Vietnamese hospitals and examine the extent to which safety attitudes vary between staff, hospitals, and health care systems. In addition, this study aimed to evaluate the psychometric properties of the instrument in Vietnamese dataset. We evaluated whether patient safety culture contributes to establish a positive patient safety culture—the cornerstone of a quality health care. In May 2015, the E-V HSOPSC was conducted with 1500 staff from 10 hospitals in Vietnam. The respondents were asked to return the completed surveys after a 3-month period. Before assessing the perceptions of health care workforce toward organizational safety culture, a confirmatory factor analysis, construct validity, and reliability were performed using SPSS and Amos 23.0. A total of 1116 questionnaires were eligible for data analysis. The outcomes from factor analysis verified the fitness and validity of the instrument. The positive response rate across 12 safety culture dimensions in the questionnaire ranged from 30% (Hospital Handoffs and Transitions) to 77% (Teamwork within Hospital Units). Overall, the mean positive score was 58.9%, which was slightly lower than of the United States. The safety was graded as “Very Good” by 52.6% of respondents in Vietnam. The E-V HSOPSC was appropriate to assess the patient safety culture in Vietnam, because the instrument provided adequate evidence of validity and reliability and patient safety culture strengths and deficiencies.