Introduction: The analgesics in current medical practice usually take hours or days to achieve relief from pain. We have recently published a preliminary report on a new analgesic method, for immediate and short-term relief of pain brought on by various dental and renal diseases. The present study investigated whether or not the method worked on other diseases, and observed the effects for a longer time, up to one hour. Methods: This randomized trial enrolled 135 patients with pain, while attending dental, renal, oncology and emergency clinics. The study was separately approved by the four participating hospitals. For the study, fist pressure (11 to 20 kg) was applied simultaneously to the back thighs for the “2-minute sciatic nerve press” and, to a parallel spot on the front thighs for the “placebo press”. Results: Pain relief averaged 43.5% (p<0.001) for the patients with various pathologies from Emergency department, but nearly 30% the patients reported no pain relief after the “sciatic press”. Significant pain relief was achieved during the 60 minutes of observation (p<0.001) for dental, renal and tumor patients. The peak pain relief for this method occurred around the 10th to 20th minutes, dropping 47% on average by the 60th minute. Conclusion: Two-minute sciatic nerve press can produce immediate significant conduction analgesia, providing a convenient, safe and powerful way to overcome pain from diverse pathologies.