OBJECTIVE: To evaluate whether patient characteristics and/or radiographic disease patterns predict symptomatic response to treatment with glucosamine in osteoarthritis (OA) of the knee. DESIGN: Exploratory prospective correlational study. SETTING: Institutional. PATIENTS: 39 participants with chronic knee pain from the local community. INTERVENTIONS: Glucosamine sulphate (1.5 g/day) for 12 weeks. MAIN OUTCOME MEASURES: Pain and physical function were assessed with visual analogue scales (VASs) and participant-perceived global change scores (GCSs). Regression modelling evaluated the relationship between treatment outcome and age, body mass index (BMI), pain and function self-efficacy and presence/absence of osteophytes in the medial and lateral tibiofemoral joint (TFJ) and patellofemoral joint (PFJ) compartments. RESULTS: 13 (33%) participants were men. The mean (SD) age and BMI were 53.6 (13.1) years and 27.9 (4.6) kg/m(2), respectively. 13 (33%), 19 (49%) and 24 (62%) participants had medial TFJ, lateral TFJ and PFJ osteophytes, respectively. Glucosamine significantly improved pain (mean change on VAS = -1.4, 95% CI -0.6 to -2.2; p = 0.002) and activity restriction (-1.9, 95% CI -1.0 to -2.8; p<0.001). At 12 weeks, 30 (77%) and 27 (69%) participants reported improvement in pain and physical function, respectively. Regression modelling showed that no evaluated variables predicted change in pain on VAS. Decreased function self-efficacy, presence of PFJ osteophytes and absence of medial TFJ osteophytes predicted functional improvement on VAS. BMI, pain self-efficacy and function self-efficacy predicted improvement in pain by GCS. CONCLUSIONS: Although glucosamine significantly improved symptoms, most of the variance in outcome at 12 weeks was unexplained by the predictors evaluated. However, glucosamine may be more effective at improving symptoms in patients with knee OA who have a lower BMI, PFJ osteophytes and lower functional self-efficacy.