Background: The World Health Organization (WHO) and the United Nations have declared the decade of 2000-2010 the “Bone and Joint Decade”. As life expectancy has increased throughout the world, musculoskeletal system disorders as osteoarthritis (OA) have emerged as important health care concerns for the elderly with considerable social and economic burden on all society, including developing countries. Materials and Methods: In order to achieve the aim of the present study, a case-control study design was adopted, and conducted in the Rheumatology Consultation Unit in Ibn-Sena Teaching Hospital in right sector of Mosul city. 200 as cases and 200 as controls were collected consecutively. Study period was from the 1st of November, 2007 to the 30th June, 2008. Data collection tool was a questionnaires used to measure general information as age in years, sex, residence, marital status and occupation. The specific information consist of history of OA, the presence of family history, history of joint trauma, stressful life events, seasonal history, the current smoking status, history of pre-existing medical disease, history of congenital anomalies and history of prolonged occupational or sport stress. Chi-square test with Odd ratio (OR) was used to the association. P-value ≤ 0.05 was considered significant. The 95% confidence interval (95% CI) were also computed. Results: The highest age-specific groups of cases was (55-64) years which constituted about 44%. The result of the present study indicated a highly positive significant association (p=0.000) between knee OA and female gender, manual working, being ever married (OR=3.94), and congenital anomalies (p=0.004). Females aged ˃45 years were prone to develop knee OA (p=0.000). A highly significant relationship was spotted regarding the history of prolonged unhealthy posture or sport stress (OR=8.27, p=0.000). Overweight and obesity are seen to duplicated the probability for knee OA. Persons with positive history of trauma were 10 times more prone to have OA. A positive association between unhealthy dietary behavior and knee OA was observed (OR=3.09). Conclusions: The OA increased steadily with age, and more in females; congenital anomalies, ever married, overweight, obesity, manual workers, history of prolong unhealthy posture or sport stress, family history, history of trauma, and unhealthy dietary behavior, all appear to play a role as risk factors in the development of knee OA.