Background: During the COVID-19 pandemic in 2020, the UK government began a mass SARS-CoV-2 testing programme. This study aimed to determine the feasibility and acceptability of organised regular self-testing for SARS-CoV-2.Methods: This was a mixed methods observational cohort study in asymptomatic students and staff at University of Oxford, who performed SARS-CoV-2 antigen lateral flow self-testing. Data on uptake and adherence, acceptability, and test interpretation were collected via a smartphone app, an online survey, and qualitative interviews.Findings: Across three main sites, 551 participants (25% of those invited) performed 2728 tests during a follow-up of 5.6 weeks. 447 participants (81%) completed at least two, and 340 (62%) completed at least four tests. The survey, completed by 214 participants (39%), found that 98% of people were confident to self-test and believed self-testing to be beneficial. Acceptability of self-testing was high, with 91% of ratings being acceptable or very acceptable. 2711 (99.4%) test results were negative, nine were positive and eight were inconclusive. Results from eighteen qualitative interviews with staff and students revealed that participants valued regular testing, but there were concerns about test accuracy that impacted uptake and adherence.Interpretation: This is the first study to assess feasibility and acceptability of regular SARS-CoV-2 self-testing. It provides evidence to inform recruitment, adherence to, and acceptability of regular SARS-CoV-2 self-testing programmes for asymptomatic individuals using lateral flow tests. We found that self-testing is acceptable and people were able to interpret results accurately.Funding: This work was funded by Oxford University Medical Science DivisionsDeclaration of Interests: LT works part-time for Sensyne Health as R&D Director and holds share options in the company. He also reports a research grant and personal fees from the company.Ethics Approval Statement: FACTS is a mixed methods cohort study conducted at the University of Oxford. It was approved by the University of Oxford Research Ethics Committee in October 2020 (CUREC ethics reference R72896/RE001).