Introduction <p>Preoperative anemia is an important target in preventing colorectal anastomotic leakage (CAL). However, it is not consistently detected and corrected in patients undergoing colorectal surgery. This study aimed to evaluate the impact of early detection and correction of preoperative anemia on perioperative outcomes and CAL.</p> Methods <p>This was a prospective subanalysis of an international open-labeled trial, which implemented an enhanced care bundle to prevent CAL after elective colorectal surgeries. It introduced interventions for early detection and correction of preoperative anemia. Primary outcome was the incidence of preoperative anemia and the effect of early correction. Secondary outcomes included the impact on CAL, postoperative course, and mortality.</p> Results <p>The study included 899 patients across eight European hospitals (September 2021–December 2023). Preoperative anemia was identified in 35.0% (<i>n</i> = 315) of participants, with 77.4% (<i>n</i> = 192) receiving iron therapy. Hemoglobin levels decreased in 4.2% (<i>n</i> = 13), remained stable in 45.8% (<i>n</i> = 143), and increased in 50.0% (<i>n</i> = 156) (<i>p</i> &lt; 0.001). Perioperative hyperglycemia was more common among patients with anemia (7.8% versus 16.4%, <i>p</i> &lt; 0.001). CAL occurred in 6.1% (<i>n</i> = 53) of patients. Anemia correction and changes in hemoglobin levels after iron treatment were not significantly associated with CAL, other complications, or mortality.</p> Conclusions <p>Early detection and correction of preoperative anemia is achievable. However, routine preoperative administration of iron alone, without concurrently optimizing other CAL risk factors, does not result in CAL prevention. Preoperative anemia indicates overall poor physiological fitness rather than being an isolated risk factor.</p> Trial number <p>NCT05250882 (20-01-2022).</p>