Introduction: Physical discomfort can include a number of symptoms such as fullness, bloating, nausea, vomiting, etc. We have recently published a new analgesic method which can produce immediate pain relief. In this study, we investigated whether or not, the method worked to relieve “non-painful discomfort”. Methods: The study was a randomized placebo-controlled trial of 53 patients with non-painful discomfort executed in a cancer care center, and an internal medicine clinic. The study was separately approved by the two participating hospitals. The non-painful discomfort reported by tumor patients occurred with late stage tumor or chemotherapy, and by patients from internal medicine clinics occurred with rheumatism, renal diseases or high fever etc. For the study, fist pressure was applied simultaneously to the back of thighs for the “2-minute sciatic nerve press”, and on the front thighs for the “placebo press”. After a baseline pain rating, doctors applied 11 to 20 kg of manual pressure for 2 minutes. Then, patients rated discomfort for a 20 min period. Results: The “2-minute sciatic nerve press” produced rapid relief of non-painful discomfort. The relief after the “sciatic press” averaged 51.9% (p<0.001) for the tumor patients, and 37.3% for the patients from the internal medicine clinic. Nearly 33% of the patients reported no relief. Conclusion: Acute sciatic nerves press can produce immediately significant relief of non-painful discomfort for short-term purposes.