OBJECTIVES: Smoking is a known risk factor for developing chronic pancreatitis and accelerates disease progression. Smoking cessation remains an important treatment recommendation, but little is known about its effects. This study evaluated smoking cessation in this population and its impact on quality of life. METHODS: Twenty-seven smokers with chronic pancreatitis participated in a smoking cessation program incorporating the QuitWorks program and individual counseling. Their smoking cessation rates were compared with a control population (n = 200) consisting of inpatients without chronic pancreatitis who smoked. Smokers were also compared with nonsmokers (n = 25) with chronic pancreatitis in terms of quality-of-life indicators. RESULTS: In 27 patients, 0 had quit smoking at 6 months, 1 at 12 months, and 0 patients at 18 months. There was a 19% quit rate in the control population at the 6-month period. Smokers had a worse quality of life, higher rates of depression and anxiety, and worse coping skills than nonsmokers. CONCLUSIONS: Smoking cessation in the chronic pancreatitis population is extremely challenging, as shown by our 0% quit rate after 18 months. Given that smokers with chronic pancreatitis also experience a worse quality of life, it becomes even more important to stress the importance of smoking cessation in these patients.