This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page page e76. Learning Objective-Upon completion of this activity, successful learners will be able to list the high resolution manometric criteria for diagnosis of achalasia types I, II, and III; list patient risk factors that could influence selection of myotomy procedure in patients with achalasia; recognize relative risks associated with the various treatment options for achalasia; and identify at least one predictive factor of successful outcome of pneumatic dilatation for treatment of achalasia. BACKGROUND & AIMS: Identification of factors associated with achalasia treatment outcome might help physicians select therapies based on patient characteristics. We performed a systematic review and metaanalysis to identify factors associated with treatment response. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library through February 21, 2019, for randomized controlled trials and cohort, case-control, and cross-sectional studies that reported patient-specific outcomes of treatment (botulinum toxin injection, pneumatic dilation, peroral endoscopic myotomy, or laparoscopic Heller myotomy). We assessed the methodologic quality of the included studies using the quality in prognosis studies tool. We planned qualitative and quantitative analyses. RESULTS: We analyzed data from 75 studies (8 randomized controlled trials, 27 prospective cohort studies, and 40 retrospective studies) on a total of 34 different factors associated with outcomes (3 demographic, 17 clinical, and 14 diagnostic factors). Qualitative assessment showed age, manometric subtype, and presence of a sigmoid-shaped esophagus as factors associated with outcomes of treatment for achalasia with a strong level of evidence. The cumulative evidence for the association with chest pain, symptom severity, and lower esophageal sphincter pressure was inconclusive. A meta-analysis confirmed that older age (mean difference, 7.9 y; 95% CI, 1.5-14.3 y) and manometric subtype 3 (odds ratio, 7.1; 95% CI, 4.1-12.4) were associated with clinical response. CONCLUSIONS: In a systematic review and meta-analysis, we found age and manometric subtype to be associated with outcomes of treatment for achalasia. This information should be used to guide treatment decisions.