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The purpose of this case series was to describe the short-term and long-term clinical effects of a manual technique for treating osteoarthritis (OA) knee pain.This study measured of the immediate effect and long-term effect by using a case series of different groups of subjects. Knee OA and activity restriction in patients were evaluated by using the Kellgren-Lawrence (K/L) Grading Scale and the Japanese Knee Osteoarthritis Measure (JKOM) index. In the intervention, lower limb muscles were squeezed by hand for 20 seconds. Each squeeze was performed for both lower limbs. Passive range-of-motion (ROM) exercise was performed on the knee joint. In one set of cases, immediate effects were measured after a one-time treatment with pretreatment and posttreatment outcome measures. Eleven people with knee OA participated in the study. On a visual analogue scale (VAS) for pain, muscle stiffness, and muscular hemodynamics for estimation of muscle blood flow were recorded before and after the squeeze-hold treatment. In another set of cases, the treatment was given to all patients once a week for 6 months, and long-term effects were measured. Data on 5 subjects with knee OA were collected for 6 months after initial treatment. The VAS for pain and JKOM were recorded every month for 6 months.For immediate effects, the VAS was 69 ± 21 mm before treatment and 26 ± 22 mm after treatment. Muscle stiffness was 8.8 ± 3.6 (absolute number) before treatment and 3.5 ± 2.1 after treatment. Tissue (muscle) oxygen saturation was 60.1 ± 5.7% before treatment and 65.3 ± 4.8% after treatment. Total hemoglobin was 24.3 ± 3.3 (absolute number) before treatment and 25 ± 2.3 after treatment. A tendency for reduction in OA knee pain and muscle stiffness was observed, and a tendency for increase was observed in the blood flow in the muscle. For long-term effects in all 5 participants (any K/L grade, any JKOM score), OA knee pain and JKOM score improved gradually through 6 months.The participants in this case series showed improvement in pain and function. These findings indicate the feasibility of a larger study on the squeeze-hold intervention for OA knee pain.