Esophageal epiphrenic diverticula (EED) are rare pulsion-type outpouchings at the lower end of esophagus. Traditionally, surgery has been performed in EED. More recently, per-oral endoscopic myotomy with septotomy (D-POEM) has emerged as an option in these cases. In this study, we aim to determine the efficacy and safety of D-POEM in cases with EED. The data of cases who underwent D-POEM in cases with EED from March 2013 to Nov 2020 were analyzed, retrospectively. The primary outcome of the study was clinical success. Secondary outcomes included technical success, procedure duration, reflux esophagitis, and adverse events. 13 patients (males 9, 48.07 ± 17.55 years) with EED underwent D-POEM during the study period. Median size of the EED was 45 mm (range 25-70). Associated esophageal motility disorder was found in 10 (76.9%) cases including type II achalasia (3), type I (3), hypercontractile esophagus (2), and unspecified (2). Technical success was achieved in 12 (92.3%) cases. Median length of total and gastric myotomies were 10 cm (range 6-20) and 3 cm (1-3), respectively. At a median follow-up of 25 months, clinical success was achieved in 84.6% cases. Mean integrated relaxation pressures reduced significantly after POEM procedure (25.80 ± 13.24 vs 9.40 ± 3.10, p = 0.001). There was one major adverse event requiring surgical intervention. D-POEM is an effective procedure in cases with EED. Long-term follow-up studies are required to ascertain the durability of response in these cases.