Purpose:To prospectively test, in a porcine model, the hypothesis that catheter-directed gastric artery chemical embolization (GACE) can result in suppression of systemic ghrelin levels and affect weight gain. Materials and Methods:This study, which had Animal Care and Use Committee approval, was performed in healthy, growing swine (weight range, 40 -45 kg; n ϭ 10). GACE was performed in five swine with the infusion of sodium morrhuate (125 g) selectively into the gastric arteries that supply the fundus. Five control animals underwent a sham procedure with 5 mL of saline. Weight and fasting plasma ghrelin levels were obtained in animals at baseline and in weeks 1-4. Statistical testing for substantial differences in ghrelin blood levels over time and between treated and untreated animals was performed by using a cross-sectional timeseries linear model with feasibility generalized least squares. Results:The pattern of the change in ghrelin levels over time was significantly different between control and treated animals (P Ͻ .004). In treated animals, ghrelin levels were significantly reduced at week 1 (mean, 664.1 pg/mL Ϯ 103.1 [standard error of the mean], P Ͻ .02), week 2 (mean, 618.1 pg/mL Ϯ 180.4, P Ͻ .001), week 3 (mean, 578.4 pg/mL Ϯ 214.9, P Ͻ .001), and week 4 (mean, 876.6 pg/mL Ϯ 228.6, P Ͻ .03) relative to baseline (mean, 1006.3 pg/mL Ϯ 190.1). The percentage change in serum ghrelin values in swine treated with GACE decreased from baseline to Ϫ34%, Ϫ38.6%, Ϫ42.5%, and Ϫ12.9% during weeks 1-4, respectively. In control swine, percentage change in serum ghrelin was Ϫ1.7%, Ϫ9.7%, ϩ2.6%, and ϩ18.2% during weeks 1-4, respectively. At the end of 4 weeks, control swine continued to gain weight, with a 15.1% increase from their original weight, while the weight in swine treated with GACE plateaued at an increase of 7.8% from the original weight. Conclusion:Catheter-directed GACE can suppress the appetite hormone ghrelin and affect weight gain.