The purpose of this paper is to explore the relationship between the use of ICT, the accumulation of e-skills, and the innovation capacities of teachers. A Web questionnaire was designed in order to examine the e-skills and the daily practices of vocational high-school teachers in Tunisia. The results and findings are based upon 288 HET respondents. A structural Equation model was developed in order to understand the main determinants of innovative pedagogical uses of ICT by HET. Two unexpected results were found. First, gender differences in terms of innovative uses are not found in Tunisia. Female HET seem to use ICT more innovatively than male ones. Secondly, we did not find a relationship between tenure or research activities of HET and their pedagogical innovative uses. However, our model shows that Computer and Internet Skills, Effective use of ICT, and Facilitation conditions play a prominent role in the innovative pedagogical use of ICT by HET in Tunisia. Findings imply that the e-learning competencies of teachers in Tunisia must be strengthened in order to reach optimal use.