Precis: Dry eye disease (DED) observed in this study is associated with ocular surface abnormalities as shown by specific dry eye tests. Changes in tear quality may be responsible for dry eye symptoms among the participants. Purpose: This study sought to evaluate DED in glaucoma patients in Ghana. Materials and Methods: This was a hospital-based descriptive cross-sectional study involving glaucoma patients on topical glaucoma treatment for at least 6 months. The medical records of participants were thoroughly reviewed for information on demographics, ocular history, medical history, number of topical antiglaucoma medications used within the last 6 months, and any other ophthalmic medications used by the participants. An Ocular Surface Disease Index (OSDI) questionnaire was administered to each participant, after which Schirmer test and tear break-up time (TBUT) were performed on each participant in a controlled environment. Results: A total of 100 individuals participated in the study. The mean±SD age of participants was 60.44±14.05 years. The majority (60.0%) of the participants were females and 55.0% of participants used 2 or more topical antiglaucoma medication. Of the participants, 81.0% reported subjective dry eye symptoms. Schirmer test and TBUT showed that 55.0% and 87.0% of the participants had decreased tear production and abnormal tear quality, respectively. Multiple logistic regression showed a significant association between age and abnormal OSDI (P=0.037), Schirmer test (P=0.003), and TBUT (P=0.042); the number of topical glaucoma medications and OSDI (P=0.016) and Schirmer test (P=0.009). The prevalence of DED was 23.0%. Increasing age was associated with an ∼7 times higher odds of having DED (P=0.0019), using >2 glaucoma medications with ∼4.5 times higher odds of having DED (P=0.001), 5 or more years of glaucoma medication use with ∼4 times higher odds of DED (P=0.009), and both benzalkonium chloride and sodium chlorite as preservative was associated with ∼3.5 times higher odds of DED (P=0.047). Conclusion: DED is prevalent among glaucoma patients in Ghana and is associated with age, duration of glaucoma medication, type of preservatives, and number of topical glaucoma medications.