IntroductionKeratoconus is a bilateral non-inflammatory ectasia, characterized by well-described histopathological changes such as stromal thinning, epithelial iron deposition, and breaks in Bowman's layer. The success of clinical intervention among patients with keratoconus is widely determined by randomized clinical trials, and despite associated difficulties, such trials may improve vision and quality of life. AimThis study aimed to assess the willingness of patients with keratoconus in Saudi Arabia to undergo clinical trials. We further aimed to identify patients' beliefs and attitudes towards clinical trials and to establish possible barriers to trial recruitment, potentially improving the quality of future clinical trials and research. Materials and methodsThis was a quantitative analytical cross-sectional study conducted between October 2020 and March 2021 among patients with keratoconus in Saudi Arabia. A self-administered questionnaire was distributed among the targeted patients. The questionnaire identified the socio-demographic characteristics of the patients and included questions on willingness, motivation, potential barriers, and helpful resources. All statistical analyses were performed using SPSS version 21 (IBM Corp, Armonk, USA). ResultsA total of 462 patients were recruited. The most common age group was 16-25 years (39.8%). There were slightly more females (51.3%) than males (48.7%). The prevalence of patients with a previous history of keratoconus was 36.8%. Results revealed that 37.2% of the patients had great motivation to take part in clinical research, and 22.3% indicated a high score in potential barriers to participation, whereas nearly 48% showed a high score in helpful resources. Statistical tests revealed that being in an older age group, having children, and possessing a higher monthly income were factors associated with increased barriers to participation in clinical research. ConclusionPatients with keratoconus showed great motivation to participate in clinical research studies and provided helpful resources. The knowledge that participation could benefit others was a primary motivator, while encouragement from other patients who participated in clinical research was the main helpful resource. Possible side effects were shown to be the major concern of the patients.