This study focuses on determining the impacts of organizational culture on the accounting information system and the operational performance of small and medium-sized enterprises in Ho Chi Minh City. The paper is organized in five parts: introduction, literature review, research methodology, research results, and conclusion and policy implications. Based on the samples of 353 respondents working in small and mediumsized enterprises in Ho Chi Minh City, the research employs both qualitative and quantitative methods to find the answers for research questions. Group discussion, which yields final observed variables of the factors of organizational culture is used for qualitative method. Statistics, assessment of the reliability of Cronbach's Alpha scale, exploratory factor analysis (EFA), confirmatory factor analysis (CFA) and structural equation modeling (SEM) are used for quantitative procedure. The results show that mission, involvement and inconsistency in organizational culture positively affect the accounting information system of small and medium-sized firms in Vietnam. In addition, mission, involvement, adaptability and consistency in organizational culture are found to have positive impacts on the firm operational performance. Another finding of the study is that the accounting information system has a positive effect on operational performance of small and medium-sized firms in Vietnam.