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This study aimed to compare the effectiveness of different amplitude-modulated frequencies of interferential current (IFC) and sham IFC on knee osteoarthritis.A randomized and single-blind study was performed on 60 patients diagnosed with knee osteoarthritis. The patients were allocated to three active IFC groups (40, 100, and 180 Hz), and one sham IFC group. Treatments were performed 5 times a week for 3 wks consecutively. Each patient was assessed at the end of the treatments and at the first month using the following measurements: visual analog scale (pain at rest, pain on movement and disability), physician and patient judgments regarding treatment effectiveness, 15-m walking time (in minutes), range of motion (ROM), the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and paracetamol intake (g/wk).Although there were significant improvements in all variables, except WOMAC stiffness and range of motion, measured in all groups at the end of the treatment and during the follow-up, this improvement was greater in active IFC groups than in the sham group. The improvement in WOMAC stiffness was observed only in active IFC treatment groups (P < 0.05). No significant difference between different amplitude-modulated frequencies of IFC treatments was observed.This study demonstrated the superiority of the IFC with some advantages on pain and disability outcomes when compared with sham IFC for the management of knee osteoarthritis. However, the effectiveness of different amplitude-modulated frequencies of IFC was not superior when compared with each other.