We reviewed our experience with 90 patients with pancreatic pseudocysts to determine if the cause of pancreatitis influenced the patients' outcome. Acute pancreatitis (AP) occurred in 57 (63%) patients due to alcoholic (n = 15), postoperative (n = 14), biliary (n = 12), and other etiologies (n = 16). Thirty-three (37%) patients had chronic pancreatitis (CP) secondary to alcohol use (n = 27) or other causes (n = 6). Multiple pseudocysts were significantly more frequent in patients with acute alcoholic pancreatitis than in patients with chronic pancreatitis (47% versus 19%, p < 0.05). Spontaneous resolution occurred within 8 weeks in 10 (11%) patients with pseudocysts (AP = 9%, CP = 15%, p = NS). However, no patient with pseudocyst associated with biliary or postoperative pancreatitis underwent spontaneous resolution. Although pseudocysts associated with chronic pancreatitis were smaller in size (8.0 +/- 4.7 versus 5.7 +/- 3.8 cm, p < 0.05), a similar proportion of them required operation compared with AP pseudocysts (56% versus 58%). There were significantly more deaths in patients with postoperative pancreatitis compared with all other groups (29% versus 7%, p < 0.05). The outcome of pseudocysts was similar regardless of size (greater than 6 cm versus less than 6 cm) and presentation (acute versus delayed). Thus, the etiology of pancreatitis was a more important determinant of pseudocyst outcome than pseudocyst size or presentation.