Background Rates of sexually transmitted infection (STI) screening are suboptimal among college women. Self-sampling methods (SSMs) may improve STI screening rates, but critical gaps remain regarding the influential characteristics of SSM to prioritize in intervention development. The purpose of this study was to explore intervention characteristics influencing the decision to adopt SSM among college women. Methods In-depth interviews (n = 24) were conducted with sexually active college women aged 18-24 years to explore preferred intervention characteristics of SSM. Interviews were stratified by screening status (screened or not screened). The instrument was guided by constructs from the Diffusion of Innovation theory and included characteristics of SSM, such as relative advantage, compatibility, complexity, adaptability, and risk and uncertainty. Results Overall, women felt that the SSM was not complex and that the instructions were straightforward. Participants discussed their strong preference for receiving their results via text or e-mail rather than via telephone. In addition, women described their concerns about mailing their sample and described their concern about potential contamination and tampering. The most salient advantage to use of SSM was avoiding an interaction with a health care provider. Conclusions This study contributes to an understanding of the salient intervention characteristics influencing the use of SSM for STI screening, which can be leveraged to improve the health of students and improve rates of screening. Findings can be used to inform the development of a future innovative, theory-based intervention that promotes the use of SSM to improve STI screening rates, and ultimately decrease the burden of STI-related disease.