BACKGROUND Balloon dilation or sphincteroplasty is emerging as a potentially safe and effective alternative to sphincterotomy in the management of bile duct stones. However, concerns related to the possible development of fibrosis or papillary stenosis led us to investigate the acute and long-term effects of balloon sphincteroplasty on papillary structure. METHODS Sixteen pigs (45 to 50 kg) underwent transduodenal cannulation of the bile duct while under general anesthesia. Balloon sphincteroplasty was performed in 10 pigs to a diameter of 8 mm at a pressure of 10 atm. Sphincterotomy was carried out in 3 pigs while 2 other untreated pigs acted as controls. Eleven animals were sacrificed at intervals from 15 to 120 minutes after balloon sphincteroplasty or sphincterotomy. The remaining 5 animals were sacrificed between 6 and 12 weeks later. Histologic sections through the papilla were assessed for evidence of morphologic changes. RESULTS When compared with controls, sections taken 15 to 120 minutes after balloon sphincteroplasty showed a progressive increase in acute inflammation extending transmurally. Intramucosal, but no transmural, hemorrhage was noted. No architectural distortion or smooth muscle disruption was observed in contrast to the transmural hemorrhage, smooth muscle disruption, and mucosal necrosis seen following sphincterotomy. After 6 to 12 weeks, mild chronic inflammation with follicular hyperplasia was present but no smooth muscle disruption or fibrosis was observed. CONCLUSION Balloon sphincteroplasty causes an acute transmural inflammatory response and chronic follicular hyperplasia but is not associated with fibrosis or altered papillary architecture.