RTI International staff brought together behavioral scientists, engineers, medical scientists, epidemiologists, and health economists to create a new audio computer-assisted self-interview (ACASI), interactive counseling and self-testing computer tool (CARE-India) to support HIV prevention research. The aims were the following: (1) Culturally adapt the CARE tool for Southern India and add functionality for fingerprint recognition and confidential linking of longitudinal risk data and automated computer interpretation of rapid HIV test results and (2) Field test the CARE-India tool among 300 participants to determine the accuracy of fingerprint identification and the accuracy of computer-assisted self-testing for HIV, and to measure the acceptability of staff assessment and testing versus the acceptability of optional ACASI assessment and computer-assisted self-testing when delivered in a general health assessment and offered with diabetes testing. CARE-India could have a large impact in this region by providing the option of HIV self-testing methodology, with improved accuracy of interpretation and documentation, and enhancing participation in HIV-related research studies.