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To examine the relationship between hormone therapy (HT) and dry-eye syndrome (DES) in postmenopausal women.A cross-sectional study was performed on 360 postmenopausal women. They were grouped into two groups. Group 1 was the control group (n = 189) without DES symptoms and which did not receive HT. Group 2 (n = 177) consisted of women with DES symptoms. Group 2 was randomly grouped into two further categories—group 2A (n = 90) that received estrogen-only HT, and group 2B (n = 87) in which participants were treated with a combination of estrogen and progesterone HT. The severity of symptom levels was determined using the Ocular Surface Disease Index levels that identify the extent of the relationship between the sex hormones and DES. A further comparison of the severity of symptoms among women using HT and those not using HT was used to establish the relationship between HT and DES in postmenopausal women.There was a significant variation in the severity levels of DES across women not using HT and those who were using HT (group 2A and 2B) (F[2, 357] = 974.186, P < 0.0001). Also, there was a significant variation in the severity levels of DES based on dosage levels (<1 and >1 mg/d) across women using HT (group 2A and 2B) (F[2, 357] = 302.513, P < 0.0001). Finally, there was a significant variation in the severity levels of DES based on duration levels 12, 36, and 48 months across women using HT (group 2A and 2B) (F[3, 356] = 218.266, P < 0.0001).The current study findings have negated the previous assumption that HT use contributes to a reduction in DES among postmenopausal women. Instead, prolonged HT use seems to increase the risk of DES.