This study aimed to compare differences of acute pancreatitis between adult- and pediatric-onset systemic lupus erythematosus (SLE) patients and to clarify the risk factors for mortality. Medical records that carried the dual diagnosis of SLE and acute pancreatitis between 1991 and 2005 were reviewed. Forty-eight episodes of acute pancreatitis were identified in 13 pediatric-onset SLE (pSLE) and 27 adult-onset SLE (aSLE) patients. The prevalence was 1.34% overall, with higher prevalence in pSLE (5.22%) compared with aSLE (0.99%) (p < 0.001). The SLEDAI score on presentation of acute pancreatitis was higher in pSLE (mean ± SD: 21.77 ± 13.09) than in aSLE patients (13.37 ± 8.32) (p = 0.05). Eleven patients died during episodes of acute pancreatitis and mortality rate was significantly higher in pSLE than in the aSLE group (53.8% and 14.8%, respectively, p = 0.015). Mortality was associated with concurrent SLE symptoms (p = 0.049), higher SLEDAI score at presentation of acute pancreatitis (p = 0.011), severe acute pancreatitis (p < 0.001), and the presence of complications (p < 0.001). The multivariate logistic regression analysis showed that severity of acute pancreatitis was the most powerful risk factor for mortality in SLE patients with this disease. In summary, our results indicate that acute pancreatitis occurs more frequently, tends to be more severe, and is associated with higher mortality in pSLE patients when compared with aSLE patient.