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In recent years, there has been greater interest and commitment in developing countries to transform their higher education (HE) using ICT. Evidence shows that ICT is underutilized by instructors in these countries. However, a rigorous context-specific model which explains this observation is currently lacking. In this large-scale study, the causal relationships among institutional and individual determinants of HE instructors' ICT use were examined in order to develop a parsimonious model. Survey data were collected from 946 instructors who were randomly selected from six Ethiopian public universities. The results of the structural equation modeling analysis indicated that solely instructors' ICT competence and ICT attitude have a direct impact on their ICT use. The study did not find support for the hypothesized direct impacts of ICT vision and plan, professional development, support, and infrastructure on ICT use. The findings of the current study imply that in developing countries, instructors’ ICT use may be improved by intervening in their professional development. Future researches need to focus on designing and assessing professional development interventions that empower instructors with ICT competence and attitude.