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Dry eye disease (DED) is an ocular surface disorder with several causes leading to numerous manifestations. It is common among medical students. This study assesses the associated risk factors and prevalence of DED and how it is impacted by prolonged reading among Saudi undergraduate senior medical students. A descriptive online selfadministered questionnaire was distributed among undergraduate senior medical students from the University of Jeddah, Saudi Arabia. Statistical Package for the Social Sciences (SPSS) version 23 was utilized to analyze the data. A total of 121 participants completed the questionnaire. They comprised 87 (71.9%) males and 34 (28.1%) females, with a male-to-female ratio of 2.6: 1. Their ages ranged from 20 to> 25 years, with the majority (54.5%) aged 20–22 years and 63 (52.1%) were fourth-year medical college students. The results showed that 22 (18.2%) had mild DED (OSDI (Ocular Surface Disease Index) score 13–22), 10 (8.3%) moderate DED (score 23–32), 45 (37.2%) severe DED (score 33–100) and 44 (36.3%) had normal (0–12) OSDI scores. The male gender, age (20–22 years) and fourth-year medical college were most common with DED. Age group 23-24 was protective against DED development with relative risk 0.264 (95% CI: 0.100-0.696, P= 0.007). Smoking and chronic disorders were not associated with DED development. DED after prolonged reading is common especially severe degree. The male gender, age group (20-22 years) and fourth-year medical students were the most affected group. Age group 23-24 was protective against …