The current research focused on examining the self-efficacy of one-to-one assistants working with students with disabilities who study in regular schools, compared to the self-efficacy of in-class teaching assistants working in special education classes in regular schools or in the special education system. The main goal of the research was to examine whether there are differences in the sense of self-efficacy between these teaching assistants and to understand the nature of the differences. Furthermore, the correlation between the sense of self-efficacy and background variables of the teaching assistants was examined: age, experience, participation in training and the kind of disability of the students they were working with have (Breyer et al. 2019; Higgins and Gulliford 2014). The sample included 291 teaching assistants in both elementary schools and high schools in Israel; 110 one- to- one assistants to students with disabilities integrated in regular classes, and 181 in-class assistants in special education. The assistants' ages range from 21 to over 51 years old and their years of work experience range from 1 year to over 11 years. A quantitative study was conducted. The data was collected using a Gibson & Dembo structured questionnaire (Gibson and Dembo, 1984), and was evaluated referring to four criteria: personal efficacy, academic efficacy, social efficacy, and emotional efficacy. The results of the research showed that there are significant differences between the two research groups. On all four self-efficacy parameters, the one-to-one assistants reported a higher sense of self-efficacy than the in-class teaching assistants. One-to-one assistants feel that they can influence a student's emotional, social, and academic performance to a greater degree than in-class teaching assistants. Furthermore, they associate the student's achievements with their own performance as teaching assistants to a greater degree than the in-class assistants. In reference to the type of disability, we found that one-to-one assistants to students with mental or behavioural disabilities reported a higher level of personal sense of self-efficacy as well as a higher level in the personal and emotional domains than those reported by in-class assistants, who work with students with the same disabilities in special education classes. A similar result was found according to social efficacy in their work with students with sensory or physical disabilities. The results of the research are important both for theory and practice. This research is preliminary, exposes us to the function of different types of teaching assistants, and presents the needs for developing systemic awareness for focusing and establishing the assistant's role, and for making it essential to involve the assistants in the educational work with children with disabilities.