The objective of the present study was to compare the effectiveness of gel and cream ibuprofen phonophoresis in patients with knee osteoarthritis. A single-blinded, randomized, comparative design was applied. Patients diagnosed with knee osteoarthritis according to the American College of Rheumatology criteria were included in the study. After obtaining written informed consent, patients were randomized into ibuprofen gel and cream phonophoresis groups. Each patient was treated five sessions per week for 2 weeks (ten sessions). Main outcome measures were 100 mm visual analogue scale (VAS) for pain and the disease-specific questionnaire; Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Sixty-one knee osteoarthritis patients with a mean age of 57.9 ± 9.7 years were included in the study. Baseline VAS and WOMAC scores were similar between gel (n = 30) and cream (n = 31) phonophoresis groups (p > 0.05 for both). Following the treatment, both groups showed improvement compared to baseline measures including VAS pain and WOMAC scores. In the gel phonophoresis group, the improvement in VAS score was higher than that observed in the cream phonophoresis group (p < 0.001). Similarly, the improvement in WOMAC total score was also higher in the gel phonophoresis group (p < 0.001). Ibuprofen phonophoresis is clinically effective in patients with knee osteoarthritis. Phonophoresis using the gel form of ibuprofen is associated with more clinical improvement than that using the cream form of the same molecule.