Objective To investigate the efficacy on clinical condition assessment and the safety of ultrasound-guided osteofascial chamber puncture manometry in evaluating the pressure of the osteofascial chamber in patients with venomous snake bites. Methods Patients with venomous snake bites admitted to the Department of Emergency Medicine of West China Hospital of Sichuan University between April 2021 and January 2023 were prospectively included, and their basic information, physiological indicators (heart rate, blood pressure), laboratory examination indicators, physical signs, treatment methods and prognosis were collected. The patients whose extremal pressure was measured by osteofascial chamber puncture under ultrasound guidance were selected as the manometry group. Patients who were bitten by venomous snakes at the same time without puncture pressure measurement were randomly selected as the control group at a ratio of 1∶1. The bleeding, infection, nerve injury, length of hospital stay and long-term prognosis of the two groups were compared to explore the safety of ultrasound-guided osteofascial chamber puncture manometry. The correlation between the pressure measured in the manometry group and creatine kinase (a representative index of acute poisoning severity score) was analyzed to explore the efficacy of ultrasound-guided osteofascial chamber puncture manometry in evaluating the disease. Results There was no significant difference between the manometry group and the control group in new or aggravated infection, bleeding, nerve injury (such as numbness and anesthesia), hospital treatment time, final detumescence time of the affected limb, or final adverse prognosis (P>0.05). There was a positive correlation between the measured pressure and creatine kinase (rs=0.286, P=0.002). Conclusions The higher pressure measured by ultrasound-guided osteofascial chamber puncture manometry is, the more serious the poisoning condition may be. In addition, ultrasound-guided osteofascial chamber puncture manometry does not prolong the hospital time of patients or the final swelling reduction time of the affected limb, and does not increase the incidence of bleeding, infection, nerve damage or eventual adverse prognosis events. It has clinical practicability and feasibility.