Introduction: Surgical exploration is still considered mandatory in the setting of small bowel obstruction (SBO) in patients without prior intra-abdominal surgery. However, recent studies have challenged this ‘classic’ approach describing success with conservative non-surgical treatment. The aim of this study is to identify clinical, radiological and biochemical variables that may be associated with the absence of intra-abdominal pathology in patients with SBO who have not undergone previous surgery. Methods: This is a retrospective cohort study of prospectively recorded data. Patients with SBO without prior abdominal surgery who presented to a single tertiary referral medical center between 2009 and 2019 were included. Results: Eighty-seven patients were included of whom 61(70.0%) were allocated to the 'therapeutic exploration' group and 26 (30.0%) to the 'non-therapeutic exploration' group. Forty-eight patients (55.0%) had adhesions, 17.2% had closed-loop obstruction, 10.0% had an internal hernia, 27.6% had bowel ischemia and 5.7% had bowel necrosis. Although multiple clinical, laboratory, radiological and preoperative factors were examined, none were significantly associated with pathological findings during surgical exploration. There was no statistically significant difference in the incidence of complications when comparing between those groups. Conclusions: In this series, no variables were associated with intra-abdominal pathology in patients who underwent surgery for SBO with no history of prior abdominal surgery. However, the fact that 27.0% had ischemic bowel upon surgical exploration suggests that this approach is still mandatory for this specific group of patients. Furthermore, clinicians and patients should be aware that negative exploration may be expected in up to 30.0%.