Background: Although HIV self-testing (HIVST) is globally accepted as an important complement to existing HIV testing approaches, South Africa has lagged behind in its adoption. As a result, data on the acceptability and uptake of HIVST testing is limited. The study investigated the acceptability of HIVST among students in Technical Vocational Education and Training (TVET) colleges in two provinces in South Africa. Methods: A cross-sectional survey using a self-administered structured questionnaire was used to collect data among 3,662 students recruited from 13 TVET colleges. Results: The mean age of the students was 21.9 years. The majority (80.9%) were sexually active; while 66.1% reported that they had one sexual partner, and 33.9% had two or more sexual partners in the past year, and 66.5% used condoms during the last sexual act. Three-quarters tested for HIV in the past year but less than half knew about HIVST prior to the survey. The acceptability of HIVST was high; about three-quarters showed a willingness to purchase a self-test kit and a majority would self-test with partners. Acceptability of HIVST was associated with being sexually active (OR = 1.73, p = 0.02, confidence interval (CI): 1.08± 2.75), having ever been tested for HIV (OR = 1.74, p = 0.001, CI: 1.26±2.38), and having multiple sexual partners (OR = 0.61, p = 0.01, CI: 0.42±0.88). Three-quarters would confirm test results at a local health facility. In terms of counselling, telephone hotlines were acceptable to only 39.9%, and less than half felt that test-kit leaflets would provide sufficient information to self-test. Interpretations: The high acceptability of HIVST among the students calls for extensive planning and preparation for the scaling up of HIVST in South Africa. In addition, campaigns similar to those conducted to promote HIV counselling and testing (HCT) should be considered to educate communities about HIVST.