Background Although there remain concerns of median nerve damage during endoscopic carpal tunnel release for carpal tunnel syndrome, carpal tunnel pressure variations during Chow's two-portal techinique have not been well investigated. Methods We performed a modified two-portal endoscopic carpal tunnel release on 30 patients by inserting a catheter pressure transducer into the carpal tunnel for continuous pressure measurement during the procedure. Grip and pinch strengths, Semmes–Weinstein monofilament test, and nerve conduction studies were examined preoperatively and at postoperative 1, 3, and 6 months. Numbness and the Disabilities of the Arm, Shoulder and Hand score were also evaluated pre and postoperatively. Findings Subjective symptoms and nerve conduction study findings improved uneventfully. The pressure was always observed to be maximum pressure immediately before the cannula was withdrawn from the exit portal, and carpal tunnel pressure > 300 mm Hg was recorded in most of the patients. Interpretation A transient increase in the carpal tunnel pressure occurred in all the patients; however, it did not correlate with their clinical outcome or with increased risk of peri-operative complications. Since time–pressure threshold of the median nerve during endoscopic carpal tunnel release is still unknown, our results did not guarantee its safety.