Objective: Patients with stage III and high-risk stage II colorectal cancer (CRC) are advised to initiate adjuvant treatment as soon as feasible and certainly before 8 to 12 weeks after resection of the tumor. A protective ileostomy is often constructed during surgery to protect a primary anastomosis "at risk", especially in rectal cancer surgery. However, up to 17% of patients with a stoma suffer from high output, a major complication that can prevent adjuvant treatment implementation or completion. To avoid delay or cancellation of adjuvant therapy after CRC resection, effective strategies must be implemented to successfully treat and/or prevent high-output stoma (HOS). Methods: We report two clinical case reports clearly demonstrating the impact and management of HOS in this setting. A review of the available literature and ongoing clinical studies is provided. Results: The clinical cases describe patients with advanced stage CRC and focus on the different strategies for HOS management, presenting their outcome and how each strategy affects the implementation of adjuvant treatment. The patient population with the highest risk of developing HOS is described, along with the rationale for using somatostatin analogs, such as lanreotide, to treat and prevent high output. Conclusion: In patients with CRC and protective ileostomies after primary resection, HOS could be treated with somatostatin analogs in combination with dietary recommendations and Saint Mark's solution. The role of this therapeutic approach as a preventive strategy in patients at high risk of developing HOS, deserves further exploration in a prospective randomized clinical trial.