Background: Premature neonates are exposed to numerous painful procedures. Physiologic fluctuations in heart rate (HR), respiratory rate, and oxygen saturation are typically used to determine the response to pain. Neurally assisted ventilatory assist (NAVA) delivers inspiratory pressure in proportion to the electrical activity of the diaphragm (Edi). Since NAVA allows self-regulation of peak inspiratory pressures (PIP), there is apprehension that painful stimulus may increase respiratory drive and result in ex- cessive PIP. This study evaluated changes in respiratory drive, measured by Edi, in response to a painful procedure (heel stick) to determine if there was excessive PIP delivered from the ventilator. Methods: Prospective, single-center study; subjects <32 weeks on NAVA/NIV NAVA requiring routine blood work via heel sticks. Vital signs were measured every 10 seconds for the first 2 minutes. PIP, Edi peak, and min were collected for the first ten breaths and then averaged at 1 and 2 minutes. Statistics were repeated measures ANOVA. Results: Fourteen subjects with gestational age 26.9+2 weeks and birth weight 994+318 grams. At study, the average age was 4.6+5 days, and weight was 948+305 grams. Following the heel stick, the first breath showed an increase in PIP and Edi peak but returned to baseline by the second breath. PIP increased again by the10th breath and at 1 and 2 minutes. HR increased after heel stick and remained elevated through the remainder of the study. There were no changes in tonic Edi, Edi min or other vital signs. Conclusion: Although the increase in PIP and Edi peak in response to heel stick pain was brief and limited, it is important always to set the PIP alarm limit appropriately to protect the lung from excessive pressures that may be generated during painful procedures.