The technology acceptance model (TAM) stipulates that both perceived ease of use (PEOU) and perceived usefulness (PU) directly influence the end user’s behavioral intention (BI) to accept a technology. Studies have found that self-efficacy is an important determinant of PEOU. However, there has been no research examining the relationship between self-efficacy and BI. The studies on the effect of self-efficacy on PU are also rare, and findings are inconsistent. In this study, we incorporate Internet self-efficacy (ISE) into the TAM as an antecedent to PU, PEOU, and BI. We conducted a controlled experiment involving a Web-based medical record system and 86 healthcare subjects. We analyzed both direct and indirect effects of ISE on PEOU, PU, and BI using hierarchical regressions. We found that ISE explained 48% of the variation in PEOU. We also found that ISE and PEOU together explained 50% of the variation in PU, and the full model explained 80% of the variance in BI.