To evaluate the effect of intraocular pressure (IOP) on the rates of macular thickness (ganglion cell layer [GCL] and ganglion cell and inner plexiform layer [GCIPL]) change over time, measured by spectral-domain optical coherence tomography (SD OCT). Retrospective cohort study. 451 eyes of 256 patients with primary open angle glaucoma (POAG). Data were extracted from the Duke Ophthalmic Registry, a database of electronic medical records of patients followed under routine clinical care at the Duke Eye Center and satellite clinics. All records from patients with a minimum of 6 months of follow-up and at least 2 good-quality Spectralis SD OCT macula scans were included. Linear mixed models were used to investigate the relationship between average IOP during follow-up and rates of GCL and GCIPL thickness change over time. The effect of IOP on the rates of GCL and GCIPL thickness loss measured by SD OCT. Eyes had a mean follow-up of 1.8 ± 1.3 years, ranging from 0.5 to 10.2 years. The average rate of change for GCL thickness was -0.220 μm/year (95% confidence interval [CI]: -0.268 to -0.172 μm/year) and for GCIPL thickness was -0.231 μm/year (95% CI: -0.302 to -0.160 μm/year). Each 1 mmHg higher mean IOP during follow-up was associated with an additional loss of -0.021 μm/year of GCL thickness (P = 0.001) and -0.032 μm/year of GCIPL thickness (P = 0.001) after adjusting for potentially confounding factors such as baseline age, disease severity, sex, race, central corneal thickness, and follow-up time. Higher IOP was significantly associated with faster rates of GCL and GCIPL loss over time measured by SD OCT even during relatively short follow-up times. These findings support the use of SD OCT GCL and GCIPL thickness measurements as structural biomarkers for the evaluation of the efficacy of IOP-lowering therapies in slowing down progression of glaucoma.