The development and integration of automated driving systems in vehicles hold substantial promise for fostering enhanced efficiency, environmental sustainability, and safety in transportation. Notably, at the lower levels of automation (LI, L2), the lane-keeping system emerges as a widely adopted automated driving feature, ensuring the vehicle’s alignment within its designated lane. With the recent introduction of new European regulations mandating the inclusion of emergency lane-keeping systems in all new vehicles starting July 2022, a growing prevalence of such systems is anticipated in the forthcoming decades. The precision and reliability of these systems in accurately detecting road markings and their distinctive features are paramount for achieving safe and intelligent mobility solutions. To fully capitalize on the advantages these systems offer, they need to expand their operational design domain. This necessitates a comprehensive understanding of their performance across diverse road design and maintenance conditions, supporting road operators in updating standards and maintenance protocols. The primary objective of this study is to investigate how various road characteristics impact the performance of lane-keeping assistant systems. Within this framework, the paper presents an experimental evaluation of Lane-Keeping System (LSS) performance conducted on two-lane rural roads. Advanced technologies for road monitoring and LSS were employed under different road and driving conditions. Through rigorous data analysis and the application of statistical models, variables significant to the fault probability of LSS were identified, highlighting the role played by horizontal curvature and driving speed. Results underscore the relevance of horizontal curvature as a critical factor constraining the physical infrastructure, shaping the operational design domain of LSS. This research contributes valuable insights toward optimizing lane-keeping assistant systems, thereby advancing the development and deployment of safe and efficient automated driving systems in diverse road scenarios.