The splanchnic vascular compartment is the major reservoir for intravascular blood volume, and dysregulation of the compartment was implicated in a series of cardiovascular conditions. We explored feasibility and effectiveness of an implantable cuff system on the greater splanchnic nerve (GSN) in healthy canines for short- and long-term neuromodulation to affect the circulation. Five mongrel hounds underwent minimally invasive right-sided unilateral GSN cuff placement. All animals underwent same day GSN stimulation and repeat stimulation at 9-30 days. Stimulation parameter optimization was conducted both acutely and chronically. Parameters ranged from 1-250 Hz, 0.25 mA-35 mA, 0.1-0.5 ms, and 30-s pulse duration. Two animals were survived for 9 days and 3 animals for 30 days. Stimulation of the right GSN increased mean arterial blood pressure by 36.9 mmHg ± 13.4 (p < 0.0001), central venous pressure by 6.9 mmHg ± 1.7 (p < 0.0001), and mean pulmonary arterial pressure by 6.3 mmHg ± 2.0 (p < 0.0001). Peak effects were observed within 30 s, and magnitude of effects was comparable between stimulation cycles (p = 0.4). Stimulation-induced changes in hemodynamics were independent of afferent nerve fibers (pain response) or the adrenal gland. Necropsy showed no evidence of nerve damage on histologic studies up to 30 days after implantation. GSN stimulation via an implanted nerve cuff provided a reproducible and rapid method to increase arterial, central venous, and pulmonary arterial pressures. The neuromodulation cuff was well tolerated and elicited a response up to 30 days after implantation. The clinical application of GSN stimulation as a tool to change central and peripheral cardiovascular hemodynamics needs to be explored.