BACKGROUND Early differentiation between septic and non-septic arthritis is difficult. A previous study showed promising diagnostic accuracy of serum Procalcitonin (PCT) in septic arthritis, limited by a low sensitive PCT test kit. OBJECTIVE To investigate the diagnostic value of PCT in patients with septic and non-septic arthritis using a novel test with low detection limit. METHODS Forty-two patients, 28 with non-septic and 14 with septic arthritis were prospectively included. For each patient, gram stain, culture and polarization microscopy of synovial fluid was done and PCT, C-reactive protein (CRP), white blood cell count, uric acid and blood cultures were taken. Patients with septic arthritis, patients with non-septic arthritis with and without concomitant infection were compared. RESULTS Patients with septic arthritis had a significant higher PCT concentration than patients with non-septic arthritis (p<0.0001). At a cut-off of 0.1 (0.25) ng/ml, sensitivity for septic arthritis was 100(93)% and specificity 46(75)%. Specificity rose to 93% after exclusion of patients with non-septic arthritis and concomitant infection. Both sensitivity and specificity for the diagnosis of septic arthritis were higher for PCT than CRP. CONCLUSIONS Our data suggest that PCT seems to be a highly sensitive and specific marker for septic arthritis, depending on the clinical setting. Further studies are warranted.