Late defecation can be a significant clinical challenge that can compromise mechanical ventilator (MV) weaning management plans and prolong an intensive care unit (ICU) stay. The purpose of this study was to explore the effect of late defecation on mechanical ventilator weaning, and the factors associated with late defecation in mechanically ventilated patients. Study design: A quantitative descriptive research design was used in this study. Sampling and setting: Purposive sample of 120 mechanically ventilated patients in three ICUs for ≥ 48 hours were investigated, and their defecation status was assessed during the first week after admission. The patients were divided into two groups: normal defecation, and late defecation. Four tools were used in this study; patient assessment sheet, acute physiology and chronic health evaluation II score, The Victoria Bowel Performance Scale, and the patient outcomes assessment tool.  Result: Incidence of weaning failure was 24.5% among patients in the normal defecation group and 52.2% among patients in the late defecation group, with a statistically significant difference (P value = 0.002*). (30.2 %) and (55.2 %) of patients in the normal defecation and the late defecation groups respectively received muscle relaxants with statistically significant difference (P value= 0.006*). Conclusion: The use of muscle relaxants, sedatives, and vasopressors may be associated factors of late defection development. Late defecation has a negative effect on MV weaning in critically ill patients. Recommendations: Frequent monitoring of gastro-intestinal motility and applying evidence based guidelines for management of disturbance in gastro-intestinal motility should be routine care in ICU.