Objective Because of the increase in the number of cases, currently, glaucoma is a significant public health issue that it leads to optic nerve damage and vision loss. High Intraocular Pressure reading indicates that the treatment given to a glaucoma patient is not sufficient/ adequate. Hence, the elevation of intraocular pressure is one of the indicators that, the therapy given to glaucoma patients under treatment is inadequate. Therefore, the main objective of the current study was to investigate predictors for the variation of elevation of IOP readings on glaucoma patients. Materials and methods A retrospective cohort study design was conducted on 1254 glaucoma patients, whose followed-ups were from September 2015 to August 2016 at Felege Hiwot Teaching and Specialized Hospital, North West Ethiopia. Data analysis was conducted using Statistical Analysis of Systems (SAS) software version 9.2 and AMOS software. The parameter estimation was conducted using the maximum likelihood estimation technique. Results Main effects like age (β = 0.01, t-value = 0.15, p-value = 0.018), patients with normal blood pressure (β = -3.35, t-value = -2.28, p-value = 0.0263), patients without diabetics (β = -3.79, t-value = -2.47, p-value = 0.014), visiting times (β = -6.00, t-value = -5.02, p-value = 0.0001), farmer glaucoma patients (β = -6.04, t-value = 3.87, p-value = 0.0001) had significant and indirect effect for the variation of elevation of IOP on glaucoma patients. Interaction effects like visiting time with existence of diabetes, visiting time with cataract surgery significantly effected on the variable of interest. Hence, both main and interaction effects had significant effects on the variable of interest. This study had identified socio-demographic characteristics, personal/individual behaviors, and clinical factors for the variation of elevation of IOP. The findings, in the current investigation, help health staff to conduct health-related education for awareness creation. Health-related education, about the progression of glaucoma, should be conducted on patients.