Introduction: The anastomotic leak (AL) is one of the most feared complications of colorectal surgery, since it is associated with a high rate of morbidity, mortality, length of hospital stay and cost of care. Our aim was to determine the risk factors associated with anastomosis leak in colorectal cancer patients who underwent surgical resection with anastomosis.

Methods: A multicentre observational, analytical, retrospective and case-control study was carried out. For each case, two controls were included from three national hospitals from Lima, Peru during the period 2021–2022. To determine the degree of association, multivariate logistic regression model was carried out.

Results: A total of 360 patients were included, 120 from each hospital. The mean age of the population was 68.03 ± 14.21 years old. The majority were 65 years old or older (66.1%), 52.8% were female, and 63.3% had clinical stage III. The 40% of the patients had albumin levels lower than 3.5 g/dL. Regarding the surgery, 96.4% were elective, 68.9% underwent open approach, and 80.8% had an operative time of more than 180 minutes. Most of them had right colon cancer (50.8%). In the multivariate analysis, a significant association was found with the age variable (OR = 2.48; 95%CI:1.24–4.97), clinical tumour level (OR = 2.71; 95%CI:1.34–5.48), American Society of Anesthesiologists (ASA) Score (OR = 3.23; 95%CI:1.10–9.50), preoperative serum albumin (OR = 22.2; 95%CI:11.5–42.9).

Conclusion: The most important independent risk factors associated with AL among patients with colorectal cancer were pre-operative such as lower preoperative serum albumin levels, followed by a higher ASA Score, clinical-stage III-IV, and an age ≥65 years old.