Background <p>Delay in diagnosing Crohn’s disease (CD) in patients presenting with perianal abscess (PAA) and/or fistula (PAF) is common. The aim of this study was to identify red flags suggestive of CD.</p> Methods <p>A systematic literature review was conducted to identify symptoms associated with CD in patients presenting with PAA/PAF. A questionnaire including those symptoms, supplemented with items from the International Organization for the Study of Inflammatory Bowel Diseases (IO-IBD) red flags index for luminal CD, was administered to all adult patients presenting with a PAF and eventually diagnosed with CD and matched patients (1:3) from the same study period with a cryptoglandular PAF (2012–2023) at a single non-academic teaching hospital. All patients were asked to recall symptoms/signs experienced during their first PAF.</p> Results <p>The systematic review identified 8 articles reporting on 15 clinical characteristics in patients presenting with PAA (<i>n</i> = 2)/PAF (<i>n</i> = 6), supplemented with 13 items from the IO-IBD red flags index (28 items in total). A total of 25 patients with CD and 75 patients with PAF without CD answered the questionnaire. Univariate analysis identified seven items associated with CD (age, family history, &gt; 2 perianal interventions, weight loss, abdominal pain, diarrhoea and fatigue), and four items remained significant in multivariate analysis: age (OR 3.4 [1.0–11.5]), &gt; 2 previous perianal interventions (OR 3.4 [1.0–10.1]), weight loss (OR 14.4 [3.7–55.6]) and abdominal pain (OR 9.8 [1.9–49.8]). Receiver-operating characteristic curve (ROC) analysis showed that a combination of these red flags was associated with good discrimination of CD versus non-CD (AUC 0.83 [0.72–0.94]).</p> Conclusions <p>The perianal red flags index has a good predictive value for early identification of patients with PAF at risk for underlying CD.</p>