Introduction The frequency and severity of abdominal pain after endoscopic mucosal resection (EMR) of colonic laterally spreading lesions (LSL) ≥20mm are unknown as are risk factors to predict its occurrence. We aimed to prospectively characterise PPE, determine the rapidity and frequency of its resolution after analgesia and estimate the frequency of needing further intervention. Methods Procedural and lesion data on consecutive patients with LSL undergoing EMR at a single tertiary referral centre were prospectively collected. If PPE, graded using a Visual Analogue Scale (VAS), lasted >5 minutes, 1 gram of paracetamol was administered. PPE lasting >30 minutes lead to clinical review and upgrade to opiate analgesics. Investigations and interventions for PPE were recorded. Results 67/336 (19.9%, 95% confidence interval [95%CI] [16.0-24.5]) of patients experienced PPE (median VAS 5, IQR 3-7). Multivariable predictors of PPE were lesion size ≥40mm, OR 2.15 (95%CI [1.14-3.48]), female sex, OR 1.99 (95%CI [1.22-3.80]) and intraprocedural bleeding requiring endoscopic control, OR 1.77 (95%CI [0.99-3.16]). 51/67 (76.1%, 95%CI [64.7-84.7]) patients with mild PPE had resolution of pain after paracetamol and were discharged without sequelae. The remainder (16, 23.9%) required opiate analgesia (fentanyl) after which 11/16 (68.8% – moderate PPE) could be discharged. 5/67 (7.5%) patients with severe PPE had no resolution despite fentanyl. All settled with hospital admission (median duration 2 days), intravenous analgesia and antibiotics. Conclusion PPE occurs in approximately 20% of patients and resolves rapidly and completely in the majority with administration of intravenous paracetamol. PPE despite opiates heralds a more serious scenario and further investigation should be considered.