BACKGROUND: Patient-reported outcome instruments are frequently used for assessing clinical outcomes after injury and surgery. Previously reported normative data for the Knee injury and Osteoarthritis Outcome Score (KOOS) are limited to a narrow subset of ages and demographics or have not included patients who do not participate in sporting activities. PURPOSE: To provide normative data for the KOOS in an 18- to 64-year-old population in the United States. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: The KOOS was administered to 999 patients or accompanying family members seen in July 2014 at an outpatient orthopaedic clinic in a suburban metropolitan city for an orthopaedic issue unrelated to their knee. Participants were eligible if they self-reported a medical history negative for knee, ankle, or hip surgery and if they did not have a current issue with their knee, ankle, or hip. Means, SDs, medians, ranges, interquartile ranges, and percentiles on the KOOS were calculated by sex, age range, laterality, and history of knee injuries in the past year. Nonparametric statistical analysis and regression analysis were used to evaluate differences in KOOS values between 5 age ranges and between those with a history of knee injuries compared with uninjured participants. RESULTS: There were 402 men and 597 women in the final study cohort. Men scored lower on the Symptoms subscale compared with other subscales (median score: 96.4 for Symptoms, 100.0 for all other subscales) in all age cohorts except the 56- to 64-year age group. Women also reported lower scores in the Symptoms subscale (median score: 96.4 for women aged 18-55 years, 92.9 for women aged 56-64 years). Median scores for the Pain and Knee-related Quality of Life subscales were lower in the 56- to 64-year female cohort (97.2 and 93.8, respectively), compared with the 18- to 55-year female cohort. The Symptoms, Pain, and Knee-related Quality of Life subscales showed the greatest variability for patients of both sexes, particularly in the youngest and oldest cohorts. Three percent of all participants reported a history of knee injuries in the past year, and all KOOS results were significantly lower (P < .05) in this population compared with uninjured participants. CONCLUSION: This study provides normative reference values for the KOOS in an 18- to 64-year-old metropolitan United States population. Study findings can aid surgeons in counseling patients and in developing expectations after the treatment of injuries.