Objectives: To investigate the analgesic effect of interferential therapy (IFT) on experimentally induced anterior knee pain. Methods: A double-blind placebo-controlled investigation was undertaken on 10 healthy subjects. Anterior knee pain was induced by an injection of hypertonic saline into the medial infrapatellar fat pad. Immediately, following the injection, subjects received 20 minutes of each of the following conditions: control, placebo IFT, 4 Hz IFT, or 100 Hz IFT, in random order on four separate days. Pain severity and the size of the painful region every 30 seconds were recorded until pain ceased. The location of the pain was recorded at 2, 7, and 12 minutes after the painful injection using a standardized figure of the knee divided into nine segments. Results: There was no effect of condition on pain severity, size of painful area, maximum reported pain severity, maximum size of painful area, duration of pain, total pain severity, and the total size of the painful area (all P > 0.09). There was no interaction between time and condition on pain severity and size of painful area (P > 0.05). However, the location of pain was more dispersed at 7 minutes in the control condition (8/9 segments) compared with the placebo, 4 and 100 Hz conditions (2/9, 1/9, and 3/9 segments, respectively). Discussion: This preliminary study indicates that IFT is not effective at reducing acute experimentally induced pain when the severity or size of the painful area is measured. However, IFT may be effective by limiting pain spreading from the source. Further research with a larger sample size is required.