Aims: Hypoglossal nerve stimulation (HNS) is currently the only FDA approved neurostimulation target for OSA. However, recent data indicate that targeted ansa cervicalis nerve stimulation (ACNS) potentially improves airflow. We compared airflow changes during targeted ANCS with HNS using a novel, percutaneous, ultrasound guided technique during drug-induced sleep endoscopy (DISE). Methods: OSA patients were fitted with a nasal mask connected to a pneumotachograph and a modified continuous positive airway pressure (CPAP) device during DISE. Ultrasound was used to identify the ansa cervicalis and the hypoglossal nerve for percutaneous placement of two temporary multi-electrode sensors. Sustained or transient periods of airflow limitation or obstruction were achieved by reducing CPAP to subtherapeutic levels. ACNS and HNS were independently applied at varying stimulus amplitudes and electrode configurations. Changes in peak inspiratory airflow (PIF) from therapeutic CPAP levels to transient CPAP reductions were compared without and with ACNS or HNS. Results: To date, 16 (4 female) participants with severe OSA (AHI=41±15 events/h), predominantly non-obese (BMI=28±3Kg/m2) were studied across 3 sites. Increases in PIF with targeted ACNS were achieved with 3.7±1.1mA stimulation. During CPAP reductions, PIF decreased to 0.17±0.12L/s. ACNS increased PIF to 0.35±0.16L/s (p<0.05). Targeted HNS increased airflow with 2.9±1.0mA stimulation. During CPAP reductions, PIF decreased to 0.12±0.10L/s and HNS increased it to 0.33±0.15L/s (p<0.05). ACNS and HNS similarly achieved PIF responses comparable to PIF during therapeutic CPAP (0.38±0.13L/s and 0.40±0.19L/s, respectively). Two participants (13%) did not show improvements in airflow with ACNS or HNS. Conclusions: Targeted ansa cervicalis and hypoglossal nerve stimulation independently restore airflow during upper airway obstruction using a novel, minimally-invasive, percutaneous insertion approach of electrode arrays during a DISE procedure for OSA patients.