Abstract: We propose a research framework to examine the determinants of nurse’s learning satisfaction in a Blended E-Learning System (BELS) environment based on task-technology fit and the technology acceptance model. The research framework integrates Task-Technology Fit (TTF), computer self-efficacy, the Technology Acceptance Model (TAM) and user satisfaction to hypothesize a theoretical model to explain and predict user’s behavioral intention to use a BELS. Self-reporting questionnaires were distributed to local community hospitals, regional hospitals and medical centers in central Taiwan. From the 900 distributed questionnaires, we received 650 completed questionnaires, yielding a response rate of 72.2%. Using Structural Equation Modeling (SEM), the results showed that perceived usefulness is an important factor affecting the behavioral intention to use a BELS. The TTF was expected to directly influence perceived usefulness. The findings provide insight into the factors that are likely to be crucial antecedents for planning and implementing a BELS to enhance nurse’s user satisfaction.