Introduction The causes of prolonged postoperative ileus (PPOI) are still unclear for major abdominal surgery, while the consequences often negatively affect the postoperative outcomes and hospitalization period. This study was performed on surgical patients with colorectal interventions, in order to investigate possible causes and therapeutic solutions for PPOI. Methods The sample of this study was represented by 236 patients admitted and operated over the past five years for colorectal tumors. Symptomatology data, paraclinical investigations, medical and surgical procedures applied have been processed from observation forms. The study included 121 men and 115 women, the average age being approximately seventy-two years. The diagnosis of PPOI was established to patients presenting (at 3 days after laparoscopic interventions, and at 5 days for open surgery) abdominal distension, flatus absence, nausea/no oral diet, and abdominal radiographic signs. Usual laboratory tests including inflammatory biomarkers (levels of leucocytes, C-reactive protein, etc.) were processed. Results On this sample of 236 patients, the data analyzed showed that 24 subjects (10,17%) developed PPOI. Open abdominal colorectal surgery, smoking history, age, male sex, and chronic pulmonary disease, were found to be independent predictive factors for PPOI. Inflammatory biomarkers were not increased statistically significant to be able to explain/justify the PPOI. For 24 patients with PPOI the average hospital staying was 21 days, compared to about 10 days of hospitalization for 212 patients without PPI. Conclusions PPOI was associated with severe complications (such as anastomotic leakage, 12,5% vs. 8,02%), and an increased hospitalization period. The main cause of PPOI is now considered surgical manipulation with subsequent inflammatory reaction; however, our study was unable to correlate inflammatory biomarkers with PPOI. Usual prokinetics had minor or no action on PPOI. New investigations should identify causes and establish possible therapeutic solutions, able to diminish/prevent the occurrence and magnitude of PPOI.