Introduction: Knee osteoarthritis (KOA) is a common musculoskeletal disorder characterized by pain, reduced quadriceps strength, and functional limitations. Blood Flow Restriction Training (BFRT) is an effective low-load strengthening technique; however, the reliability of manual manometer-based BFRT cuff pressure measurement in individuals with KOA remains inad equately investigated. Aim/Objective: To determine the intra-rater and inter-rater reliability of manual BFRT manometer cuff pressure measurements and monitor physiological responses during cuff application in individuals with mild to moderate KOA. Methods: A methodological observational reliability study was conducted on 30 participants aged 40–60 years with mild to moderate KOA selected through convenience sampling. BFRT cuff pressure was measured using a manual manometer-based system. Two independent raters recorded cuff pressure over three trials. Physiological responses, including pulse rate, oxygen saturation (SpO2 ), Numerical Pain Rating Scale (NPRS), discomfort level, and skin discoloration, were monitored. Intra-rater and inter-rater reliability were analyzed using Intraclass Correlation Coefficients (ICC), while Cohen’s Kappa assessed agreement for physiological observations. Results: Excellent intra-rater reliability (ICC=0.93) and good-to-excellent inter-rater reliability (ICC=0.89) were observed. Low Standard Error of Measurement (SEM) and Minimal Detectable Change (MDC) indicated high measurement consistency. Physi ological monitoring showed only mild discomfort and pain, with stable SpO2 and pulse rate, no abnormal skin discoloration, and no vascular complications. Cohen’s Kappa values ranged from 0.85 to 0.95, indicating almost perfect agreement. Conclusion: Manual manometer-based BFRT cuff pressure measurement demonstrated excellent reliability and physiological tolerability in individuals with mild to moderate KOA, supporting its clinical use in physiotherapy, particularly in resource-limited settings.