Introduction: The advent of endoscopic ultrasound (EUS)-guided celiac plexus block (CPB) and celiac plexus neurolysis (CPN) has provided immeasurable benefit for patients with pain from chronic pancreatitis and pancreatic malignancies. There are differences in efficacy based on indication and protocol used for CPN and CPB. Here we aim to characterize efficacy, safety, and variations in protocol of both EUS-guided CPB and CPN by performing a systematic review of the literature. Methods: Using predefined keywords a search was performed using the EMBASE, Medline, and Cochrane databases through January 2018. Abstracts that discussed the outcomes of EUS-guided CPN and/or CPB were considered for inclusion. Data was abstracted from all papers, including demographic information, indication for CPN and CPB, protocol used for CPN and CPB, outcomes of intervention, and complication rates of endoscopy. Weighted data was used to calculate the efficacy and complications. Results: Following a database search, 437 abstracts were reviewed. 35 studies were selected for data abstraction of which 8 were randomized trials, 16 prospective, and 11 retrospective. 1290 patients underwent CPN and 714 underwent CPB. In those undergoing CPB and CPN, the main indications were chronic pancreatitis (98%, 698/714) and pancreatic cancer (99%, 1278/1290) respectively. In studies reporting the rate of response, overall initial response was 64% (873/1369). CPN and CPB had an initial response rate of 65% (482/745, range 25-100%) and 63% (391/624, range 0-100%) respectively. When celiac ganglia were targeted, response was 74% (68/92, range 65-94%). Duration of response varied widely across all studies and interpretation was limited by duration of follow-up. No deaths or perforations were reported. There was 1 upper gastrointestinal bleed and 1 peri-pancreatic abscess attributed to the intervention. The most common side effects were transient diarrhea and transient hypotension. In regards to anesthetic agents used, bupivacaine 0.25-0.75%, lidocaine 1.0-2.0%, and xylocaine 1.0% were all used. Triamcinolone was used in doses ranging from 40-160 mg. Finally, alcohol 95-99% was used in doses ranging from <5 ml to 20 ml. One study looked at the efficacy of phenol 7% as a neurolytic agent in those intolerant of alcohol. Conclusion: Overall, CPB and CPN appear to be effective and safe modalities at controlling pain. Due to variations in protocol, clinical guidelines are required to outline best-practice for both EUS-guided CPB and CPN.