Introduction Anastomotic leakage (AL) is one of the most severe complications following rectal cancer (RC) surgery, with significant implications for morbidity, mortality, and oncological outcomes. Identifying risk factors associated with AL may enhance surgical decision-making and improve patient prognosis. Methods A retrospective cohort study was conducted, including 42 adult patients who underwent RC resection at a hospital in Mexico City between January 2015 and December 2022. Demographic, clinical, pathological, and surgical variables were analyzed to assess their association with AL. Univariate and multivariate statistical analyses were performed to identify independent risk factors. Results The overall incidence of AL was 11.9%, consistent with previous literature. Univariate analysis revealed no significant differences in patient-related factors such as age, BMI, ASA classification, diabetes mellitus, smoking, or biochemical markers (p>0.05). Treatment-related factors such as neoadjuvant therapy and diverting stoma (DS) placement did not show a significant association with AL. However, surgical factors played a crucial role: operative time was significantly longer in patients with AL (349.0 vs. 232.9 minutes, p=0.024), intraoperative blood loss was markedly higher (800.0 vs. 198.6 mL, p<0.001), and transfusion rates were elevated (60.0% vs. 13.5%, p=0.040). Tumor location in the middle rectum was more frequent among AL cases (60.0% vs. 18.9%, p=0.090). Postoperative complications were significantly more severe in patients with AL, with prolonged hospital stays (20.0 vs. 10.2 days, p=0.043) and increased reintervention rates (80.0% vs. 5.6%, p<0.001). In the logistic regression model, none of the analyzed variables reached statistical significance (p>0.99). However, operative time showed an odds ratio (OR) of 1.736 (p=0.997), suggesting that for each additional minute of surgery, the risk of AL could increase by 73.6%. Despite this trend, the wide confidence interval limits its precision and clinical applicability. Age showed an OR of 0.023 (p=0.998), potentially suggesting a 97.7% reduction in leakage risk for each additional year, although this result was not statistically significant and should be interpreted with caution. Conclusion Although no statistically significant risk factors were identified in the multivariate analysis, intraoperative variables such as prolonged surgical time, high blood loss, and transfusion requirement emerged as clinically relevant trends. These findings emphasize the need for optimizing surgical techniques and perioperative management to mitigate AL risk. Further studies with larger sample sizes are necessary to validate these associations and improve risk stratification models.