Study objective: Ultrasound guidance does not eliminate the risk of intraneural injection, which must be avoided during PNB. Combining ultrasound guidance (USG), nerve stimulation (NS), and injection pressure monitoring is advocated to prevent nerve injury during PNB. We hypothesized that combining patient-tailored dynamic NS and real-time pressure sensing (RTPS) could reduce the incidence of intraneural injection and nerve puncture during USG PNB compared with a traditional fixed thresholds (Control) procedure.Design: Randomized, prospective study.Setting: Operating room.Patients: One hundred ASA physical status I to III patients undergoing orthopedic surgery.Interventions: Patient anesthetized using axillary, sciatic or femoral USG PNB were randomized to the PresStim group (Dynamic RTPS and NS set at 1.5 mA then decreased; n = 50) or Control group (fixed thresholds for in-line pressure mechanical manometer and NS at 0.2 mA; n = 50).Measurements: Procedural ultrasound images and videos were recorded, stored and reviewed in random order by two experts in ultrasound-guided PNB blinded to the group. They noted the needle-to-nerve relationship and intraneural injection for all blocked nerves.Main results: One hundred and twenty-three USG PNBs were performed (56 axillary brachial plexus blocks, 40 femoral nerve blocks and 27 sciatic popliteal nerve blocks); 235 blocked nerves and videos were recorded and analyzed (PresStim, 118; Control, 117). Less paresthesia was noted in the PresStim group (12.7%) compared with the Control group (18.8%). The risk of intraneural injection was significantly higher in the Control group (odds ratio [OR], 17.1; 95% confidence interval [CI], 2.2-135, P = 0.007). The risk of nerve puncture (OR, 22.7; 95% CI, 2.9-175, p = 0.003) and needle-nerve contact (OR, 4.7; 95% CI, 2.4-9.5, p < 0.001) was significantly higher in the Control group than the PresStim group.Conclusions: Under the conditions of the study, dynamic triple monitoring combining RTPS, NS and USG decreases intraneural injection and unintentional needle-nerve contact and puncture during a PNB procedure.