Negotiation of meaning refers to intricate processes through which interlocutors can modify their speech to ensure the production and reception of comprehensible input. This empirical study aimed to thoroughly investigate the multifaceted aspects of negotiation of meaning and identify the influential factors shaping this process during classroom interactions within an English for Medical Purposes (EMP) class at a medical college in Saudi Arabia. Employing an eclectic qualitative methodology that incorporates key principles of Linguistic Ethnography, this research presented a comprehensive analysis of data collected throughout the entire fall semester of the academic year 2020/2021. The rich dataset stemmed from meticulous observations of ten EMP classroom sessions. Findings from this study shed light on the teacher's strategic employment of various techniques, including confirmation checks, comprehension checks, clarification requests, and other forms of repairs, to effectively negotiate meaning in the classroom. Moreover, the investigation underscores the significance of factors such as familiarity with topics, students' proficiency levels, and nature of tasks undertaken, as critical determinants influencing the negotiation of meaning in classroom interaction. By emphasizing the positive and essential role of negotiation of meaning, this study underscores its contribution to optimizing input comprehensibility and enhancing overall classroom interactions.