Background <p>Endoscopic procedures for post-pyloric feeding include percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) and direct percutaneous endoscopic jejunostomy (PEJ). We conducted the largest and only dual-center retrospective study comparing outcomes of patients receiving PEG-J vs. PEJ.</p> Methods <p>A dual-center retrospective study was conducted of patients who underwent either PEG-J or PEJ for post-pyloric feeding ±  gastric decompression. Primary outcomes were technical success (TS) and reintervention for adverse event (rAE: ≥ 1 feeding tube exchange, conversion, and/or removal performed as needed for management of tube-related or stoma-related AE). Secondary outcomes were index procedure time, AE category (tube-related/stoma-related), and reintervention(s) prompted by each AE category.</p> Results <p>TS was similar for both procedures (PEG-J: 71/75 [95%] vs. PEJ: 68/75 [91%], <i>p</i> = 0.533). The PEG-J cohort had more reinterventions for AEs (rAE: 33/75 [44%] vs. 20/75 [27%], <i>p</i> = 0.04) occurring closer to the index procedure (median time to rAE, 163&#xa0;days vs. 307&#xa0;days, log rank <i>p</i> = 0.018). Tube-related AEs (38/75 [51%] vs. 25/75 [33%], <i>p</i> = 0.047) and resultant reinterventions were more common after PEG-J, especially tube clog (<i>p</i> = 0.017) and retrograde J-tube migration (<i>p</i> = 0.0003). Stoma-related AEs (PEG-J: 3/75 [4%] vs. PEJ: 7/75 [9%], <i>p</i> = 0.327) and resultant reinterventions were similar in both cohorts.</p> Conclusions <p>Technical success was comparable between PEG-J and PEJ; however, PEJ recipients had fewer tube-related AEs and resultant reinterventions. These findings favor PEJ as first-line for patients requiring prolonged post-pyloric feeding, especially if concomitant gastric decompression is not required.</p> Graphical Abstract <p></p>