Background: Endoscopic snare papillectomy (ESP) has been established as a safe and effective treatment for ampullary adenomas. However, little is known about the optimal post-procedure follow-up period and the role of routine endoscopic surveillance biopsy following ESP. We aimed to evaluate patient adherence to a 5-year endoscopic surveillance and routine biopsy protocol after ESP of ampullary adenoma. Methods: We reviewed our prospectively collected database (n = 98), all members of which underwent ESP for ampullary lesions from January 2011 to December 2016, for the evaluation of long-term outcomes. The primary outcome was the rate of patient adherence to 5-year endoscopic surveillance following ESP. The secondary outcomes were the diagnostic yield of routine endoscopic biopsy, recurrence rate, and adverse events after endoscopic surveillance in the 5-year follow-up (3-month, 6-month, and every 1 year). Results: A total of 19 patients (19.4%) experienced recurrence during follow-up, all of these patients experienced recurrence within 3 years of the procedure (median 217 days, range 69–1083). The adherence rate for patients with sporadic ampullary adenoma were 100%, 93.5%, and 33.6% at 1, 3, and 5 years after ESP, respectively. The diagnostic yield of routine endoscopic biopsy without macroscopic abnormality was 0.54%. Pancreatitis occurred in four patients (4%, 3 mild, 1 moderate) after surveillance endoscopic biopsy without macroscopic abnormality. Conclusions: Given the low 5-year adherence rate and diagnostic yield of routine endoscopic biopsy with risk of pancreatitis, optimal surveillance intervals according to risk stratification (low grade vs. high grade adenoma/intramucosal adenocarcinoma) may be required to improve patient adherence, and routine biopsy without macroscopic abnormality may not be recommended.