Cardiovascular disease is the leading cause of mortality in patients with diabetes mellitus (DM). We sought to establish for the first time in Saudi Arabia an intravascular ultrasound (IVUS) profile of DM patients with acute coronary syndrome (ACS). Patients and methods: We retrospectively analyzed 210 IVUS studies in 181 patients hospitalized in King Salman Heart Centre for ACS. IVUS was performed to guide percutaneous coronary interventions (PCI) of borderline moderate lesions. Results: Mean age was 58 ± 10 years, 78% (n = 163) of IVUS studies were performed in men. There were 71% (n = 128) patients with DM. ST elevation myocardial infarction (STEMI) was the most common clinical presentation (47%, n = 88 patients). As compared to non-DM, the intermediate lesions of DM patients had a significantly larger IVUS plaque volume (267 ± 174 mm3 versus 193 ± 111 mm3, p < 0.01), vessel volume (496 ± 314 mm3 versus 358 ± 182 mm3, p < 0.01), lumen volume (231 ± 156 mm3 versus 164 ± 88 mm3, p < 0.01) and longer lesions (37 ± 12 mm versus 30 ± 8 mm, p < 0.01). A positive remodelling index was observed for patients with and without DM, without significant difference (1.4 versus 1.3 respectively, p = 0.7). Percent plaque volume and obstruction were not different. Conclusion: IVUS demonstrates longer lesions to be treated in DM patients with ACS in Saudi Arabia, however no difference in average plaque burden or remodelling index. These findings are likely to impact our understanding of optimal PCI strategies in DM patients.