Background: Laparoscopic sleeve gastrectomy (LSG) is a common weight loss operation that is increasingly being managed on an outpatient or overnight stay basis. The aim of this systematic review was to evaluate the available literature and develop recommendations for optimal pain management after LSG. Methods: A systematic review utilizing preferred reporting items for systematic reviews and meta-analysis with PROcedure SPECific Postoperative Pain ManagemenT methodology was undertaken. Randomized controlled trials (RCTs) published in the English language from inception to September 2018 assessing postoperative pain using analgesic, anesthetic, and surgical interventions were identified from MEDLINE, EMBASE and Cochrane Databases. Results: Significant heterogeneity was identified in the 18 RCTs included in this systematic review. Gabapentinoids and transversus abdominis plane blocks reduced LSG postoperative pain. There was limited procedure-specific evidence of analgesic effects for acetaminophen, non-steroidal anti-inflammatory drugs, dexamethasone, magnesium, and tramadol in this setting. Inconsistent evidence was found in the studies investigating alpha-2-agonists. No evidence was found for intraperitoneal local anesthetic administration or single-port laparoscopy. Conclusions: The literature to recommend an optimal analgesic regimen for LSG is limited. The pragmatic view supports acetaminophen and a non-steroidal anti-inflammatory drug, with opioids as rescue analgesics. Gabapentinoids should be used with caution, as they may amplify opioid-induced respiratory depression. Although transversus abdominis plane blocks reduced pain, port-site infiltration may be considered instead, as it is a simple and inexpensive approach that provides adequate somatic blockade. Further RCTs are required to confirm the influence of the recommended analgesic regimen on postoperative pain relief.