Purpose: Anastomotic leak (AL) following oesophagectomy results in major patient morbidity and increased resource utilisation. While multimodality therapy improves survival, treatment-related toxicity may increase the risk of perioperative complications. Identifying modifiable risk factors for AL is therefore critical to reducing postoperative morbidity. We examined risk factors for AL and quantified its clinical impact in a high-volume Australian centre. Methodology: Patients undergoing curative-intent oesophagectomy with gastric conduit reconstruction for oesophageal or gastro-oesophageal junction cancer between 1993 and 2022 were identified from a prospectively maintained database. AL was defined using Esophagectomy Complications Consensus Group criteria. Risk factors were assessed using univariate and multivariate logistic regression. Results: Among 1,219 patients, AL occurred in 11% (131/1219). Patients who developed AL experienced substantially greater morbidity, with a longer median hospital stay (24 vs 13 days, p<0.01) and higher reoperation rates (16.8% vs 5.8%, p<0.01). On univariate analysis, male sex, preoperative weight loss >20%, clinical nodal stage cN2, and higher radiotherapy dose were associated with AL. Compared with 35 Gy, radiotherapy doses of 41.4 Gy (OR 2.8, 95% CI 1.25–6.48) and 45 Gy (OR 3.1, 95% CI 1.23–7.99) were associated with an increased risk of AL. On multivariate analysis, preoperative weight loss >20% remained independently associated with AL (OR 3.7, 95% CI 1.63–7.92). Conclusion: Anastomotic leak is associated with significant postoperative morbidity following oesophagectomy. Severe preoperative weight loss is an independent and potentially modifiable risk factor for AL. Targeted nutritional optimisation and careful radiotherapy planning may reduce anastomotic complications and their downstream clinical impact.