Purpose/Objective(s): Ampullary and Periampullary carcinomas (APAC) are uncommon gastrointestinal cancers that are often amenable to surgical resection. The benefit of postoperative adjuvant chemoradiotherapy (ACRT) in patients with completely resected localized AC has been controversial. A meta-analysis which was conducted in 2017 found no associated survival benefit for adjuvant therapies in APAC. However, this meta-analysis combined studies that used adjuvant chemotherapy alone with those that used ACRT. The purpose of this meta-analysis is to evaluate the impact of ACRT on the overall survival (OS) of patients with completely resected APAC incorporating more recent studies. Materials/Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of (i) resected Ampullary and Periampullary carcinoma (ii) English language (iii) publication date starting 1999 to the present, (iv) studies reporting OS with hazard ratios (HR) or Kaplan-Meier curves of patients that underwent ACRT versus those that did not, and (v) studies that reported the aggregate OS data of adjuvant therapies where the preponderance of the cohort received ACRT. Adjuvant chemotherapy studies and those that reported aggregate OS for a cohort with a preponderance of adjuvant chemotherapy were excluded. A meta-analysis was conducted using an inverse variance method with a random-effects model. Results: Sixteen studies that included 1,122 patients treated with ACRT were analyzed. The majority of APAC patients that received ACRT tended to have high-risk features. These high-risk features included T3/T4 primary tumors, positive regional lymph nodes, poor histologic differentiation, and positive resection margins. Four of these studies analyzed their OS data for the high-risk APAC patients in addition to the cohort as a whole. Intra-arterial chemotherapy and concomitant radiotherapy were used in one study. ACRT was found to be significantly associated with OS benefit in patients with completely resected APAC (HR 0.76, 95%CI: 0.65-0.88, p<0.001) with an inconsistency estimate, I2 = 37% (95%CI: 0-65). Conclusion: This is the first meta-analysis to show that adjuvant chemoradiotherapy is associated with a survival benefit in patients with completely resected high risk Ampullary and Periampullary carcinoma. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the use of ACRT in this patient population.