As morbidity and mortality rates for pancreatic surgery have improved over the past decades, patients with major medical comorbidities have been considered for operative treatment. The influence of poor health status on operative morbidity in patients with chronic pancreatitis is evaluated in this study. The records of 313 consecutive patients who underwent pancreaticoduodenectomy (n = 78), distal pancreatectomy (n = 83), or lateral pancreaticojejunostomy (n = 152) for chronic pancreatitis were retrospectively reviewed and analyzed. Patients' risk for adverse outcome resulting from overall health status was audited using age, comorbidities, and Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) physiological score. Univariate analysis showed that patient's age did not contribute to change in morbidity (odds ratio [OR] = 1.01, P = 0.59). The presence of cardiac disease but not other comorbidities increased adverse outcome affected the need for intensive care unit stay and length of hospital stay (morbidity: 29% vs. 51%, OR = 2.6, P = 0.003). POSSUM physiological score was associated with an increase in morbidity and mortality (morbidity: OR = 1.16, P = 0.001; mortality: OR = 1.49, P = 0.001), in particular intraabdominal abscesses. Multivariate analysis showed that the only variable independently correlating with perioperative complications was POSSUM physiological score. Single comorbidities do not independently influence outcome after operations for chronic pancreatitis. A combination of several comorbidities is associated with an increase in postoperative infectious morbidity and mortality. High-risk patients should not be excluded from operative treatment, but need to be closely selected on a case-by-case basis.