Purpose. To examine the relationship between physical activity and ocular perfusion pressure (OPP), a consistent risk factor for glaucoma. Methods. The relationship between previous physical activity and current OPP in 5650 participants aged 48 to 90 who attended the first (1993-1997) and third (2006-2010) health check as part of the European Prospective Investigation into Cancer (EPIC)-Norfolk study was examined. Usual combined physical activity at work and leisure was assessed using a validated instrument. Individuals were categorized as inactive, moderately inactive, moderately active, or active. Three IOP measurements were obtained (Ocular Response Analyzer [ORA]; Reichert, Inc., Depew, NY). Mean Goldmann correlated IOP (IOPg) from one eye was used in the analysis. Systolic and diastolic blood pressure (BP) were recorded as the mean of two measurements taken with a sphygmomanometer. Associations between physical activity and low (≤40 mm Hg) mean OPP (2/3 mean arterial pressure - IOP) and low (≤50 mm Hg) diastolic OPP (diastolic BP - IOP) were tested using logistic regression, adjusting for age, sex, body mass index, social class, IOP, and BP. Results. Active people had a lower risk of mean OPP ≤ 40 mm Hg and diastolic OPP ≤ 50 mm Hg after adjusting for age, sex, social class, and body mass index (odds ratio, 0.75; 95% confidence interval [CI], 0.60-0.93; P < 0.01) and (odds ratio, 0.73, 95% CI, 0.58-0.93; P = 0.01), respectively. The association between physical activity and perfusion pressure was independent of IOP, but largely mediated through diastolic BP. Conclusions. Lower levels of physical activity were associated with lower OPP. Further research is needed to investigate the potential benefit of increased physical activity as a safe and simple method of modifying glaucoma risk.