Taxes are levied in almost every country, primarily to raise revenue for government expenditures. This study explores factors influencing tax compliance of small- and medium-sized enterprises (SMEs) in Vietnam. Data from 376 SMEs, who are business taxpayers, were collected through a researcher–administered questionnaire survey method. The results indicate that six groups of factors have significant impacts on tax compliance among Vietnamese SMEs. These groups include: Business characteristics (BC), Characteristics of accounting practices within organization (AP), Awareness of tax obligations (TO), Tax policy (TP), View on tax compliance (TC), and Probability of tax examination on taxpayer compliance (TE). Multivariate analysis was adopted; Cronbach’s alpha coefficients were calculated, then, Exploratory Factor Analysis (EFA) was used. The findings show that, among these six factors, the most influential is Characteristics of accounting practices (AP). Thus, it is recommended that tax agencies should help SMEs improve their accounting skills and increase their knowledge by organizing training workshops and short courses on taxation. SMEs also need to have an adequate accounting system in accordance with principles and standards prescribed by the Tax Law. It is expected that this study can provide important insights and understandings to policy-makers, practitioners, academicians and other regulatory authorities in tax policy formulations.