Introduction: Osteoarthritis (OA) of the knee is the most common type of arthritis of the elderly among Asians. Reports suggest that it affects the quality of life. Hence, this study was undertaken with the objective to know the impact of OA of the knee on 8 domains of health related quality of life (HRQoL) which include: (1) Physical functioning (PF), (2) role limitation due to physical health (RP). (3) Emotional well-being/mental health (MH), (4) role limitation due to emotional problems (RE), (5) energy/vitality, (6) social well-being (short form [SF]), (7) body pain, (8) general health. Materials and Methods: This cross-sectional study was conducted in primary care rural clinics situated on peripheral areas of Mangalore city. Total sample size was calculated to be 77. Patients who met the criteria of modified American Rheumatologic Association Classification for OA of knee were administered a SF- 36 questionnaire to measure the HRQoL in the local language version. Mean scores (with its standard deviation) across each domain was calculated. Results: Of 80 patients, 38 were males. OA affected HRQoL. Four out 8 factors had more impact on HRQoL (they are PF, RP, MH, RE). Duration of OA is an important determinant on HRQoL. Patients with newer onset of OA (<4 years) had less physical impact on (Domain, Mean) (PF, 54.36; RP, 13.5) and more emotional/mental impact (MH, 28.23; RE, 59.13). With increasing duration (>4 years) of OA (Domain, Mean), the emotional impact (MH, 44.67; RE, 45.67) reduced but the physical impact (PF, 47.83; RP, 19.75) persisted/got worse. Conclusion: Osteoarthritis had impact on HRQoL. Duration of OA determines the kind of impact. With the onset of OA emotional/mental support would be needed in addition to the medical treatment. As the disease progresses, they tend to cope with emotional/mental problems even as the physical problems persist/increase.