Long-term effects of shockwave lithotripsy (SWL) are unknown; however, we recently found an association between SWL and diabetes mellitus in a population based case control cohort. To further study the association between SWL and diabetes mellitus, we determined the immediate impact of SWL on the pancreas as well as the long-term natural history of stone disease following treatment. Chart review identified 630 patients treated with SWL at our institution in 1985. Questionnaires focusing on recurrent stone episodes after SWL were sent to 578 patients alive in 2004. To further assess impact of SWL on the pancreas, pancreatic enzyme measurements were performed on 24 symptomatic stone patients treated in 2006 with ureteroscopy (n=12) and SWL (n=12). Serum amylase and lipase were evaluated pre and post SWL. A≥5 U/L increase in either lab value was considered significant. Among patients in the long-term SWL treatment group, the questionnaire response rate was 58.9% (288/489). Recurrent stone events were noted in 154 (53.5%) of the survey respondents. Characteristics associated with stone recurrences were: gender (p=0.004), age at SWL (p=0.022), BMI (p=0.007), SWL complications (p=0.009), and lower pole SWL (p=0.025). Recurrent stone disease was also associated with the development of diabetes mellitus (p=0.020). In the contemporary group of treated stone patients, pancreatic enzyme analysis demonstrated an increase in serum amylase and lipase in 3 (25.0%) SWL patients and 1 (8.3%) ureteroscopy patient (p=0.273). In conclusion, over half of the patients treated with SWL will develop recurrent stone events. We found a strong association between recurrent stone disease and the development of diabetes mellitus at long-term follow-up. Although not statistically significant due to small number, data in a contemporary treatment cohort suggest the possibility that the pancreas can be adversely affected by SWL.