OBJECTIVE: This study explored the association of patients' demographics, health status, symptom severity, previous osteoarthritis (OA) care, and psychological status with the change in pain severity following a first-line intervention including education and exercise for OA provided nationwide in Swedish primary care. METHODS: This register-based cohort study included 23,309 people with knee or hip OA from the Better Management of Patients with OA register. Linear regression models were used to assess the association of independent variables with the change in pain from baseline to 3 and 12 months. All the analyses were stratified based on the affected joint (hip vs knee). RESULTS: In people with hip and people with knee OA, high levels of baseline pain were associated with decreased pain at both follow-ups (3 months: knee B = -.67; hip B = -.64; 12 months: knee B = -.70; hip B = -.66), whereas being older, overweight, or female had a weak or no association. Finally, at both follow-ups, bilateral OA was associated with increased pain only in people with knee OA, whereas comorbidities and the willingness to undergo surgery were associated with increased pain regardless of the affected joint. CONCLUSIONS: Baseline pain showed the strongest association among the analyzed variables, whereas sex, age, and body mass index appear to be weakly associated with the pain change after a first-line intervention. Comorbidities and willingness to undergo surgery showed a potentially important association and may have a negative impact on the pain change following a first-line intervention. IMPACT: In people with hip or knee OA, age, sex, body mass index, and previous surgery are only weakly associated with the change in pain after a first-line intervention supporting the evidence recommending exercise and education as a foundation for all OA therapy. Having comorbidities and being willing to undergo surgery is associated with a worse outcome from a first-line intervention, including exercise and education. Individualized treatments addressing the disease perception and the specific comorbidity profile may improve the outcomes.