Background/Aims: Colorectal cancer (CRC) is the most frequent cancer and a leading cause of cancer death in the Kingdom of Saudi Arabia (KSA). To date, no nationwide screening programs have been adopted. This prospective, longitudinal study investigated factors influencing the outcome of CRC in Saudi patients. Methods: Patients completed a CRC awareness questionnaire. Colonoscopy, CT/MRI, histopathology of tumor biopsies, and KRAS and BRAF testing were performed. Patients were treated according to their stage. All patients were followed until the end of the study and 3- and 5-year survival was assessed. Results: Sixty percent of study patients with sporadic CRC presented with significantly advanced disease (stages III and IV) with or without metastases at entry. Patients showed low levels of awareness of the risk factors and signs of CRC. Patients presented at a median age of 50 years. Family history of CRC and ulcerative colitis were positive in 11 and 6% of patients, respectively. Stage III/IV tumors with distant metastases at enrollment, right-sided tumors, mucinous tumors, lymphovascular invasion, and KRAS (51%) or BRAF (28%) mutations predicted poor prognosis and survival. Conclusion: CRC in KSA is usually diagnosed at advanced stages with metastases and KRAS/BRAF, and is associated with poor prognosis and short survival. Nationwide awareness campaigns and screening programs for CRC are critical for prevention, early detection and adequate management of CRC.