Background and Purpose: Intracranial atherosclerosis is an important cause of ischemic stroke and even mild stenosis or subtle wall changes may be a marker for subsequent stroke risk. We tested whether any arterial wall irregularity was predictive of recurrent stroke in participants of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial. Methods: SPS3 was a randomized trial investigating optimal blood pressure target and antiplatelet regimen in patients with recent, symptomatic, MRI-confirmed lacunar stroke patients. Magnetic resonance angiography (MRA) proximate to study entry was adequate and available for 2169 of 3020 study patients. Seven intracranial arteries (basilar [BA], vertebral [VA], internal carotid [ICA], and middle cerebral artery [MCA]) were assessed on time-of-flight MRA for wall irregularities including stenosis and changes of arterial diameter. Cox Proportional Hazards models adjusted for assigned treatments and clinical risk factors were used to estimate risk for recurrent stroke associated with any wall irregularity overall and in specific arteries. Results: Mean age of the 2169 patients was 63 yr with 63% male; hypertension, diabetes, and prior lacunar stroke were present in 75%, 36%, and 10%, respectively. Wall irregularities in ≥1 artery (325 one artery, 250 > 1 artery) were observed in 575 patients (27%). Recurrent stroke occurred in 195 patients during mean follow-up of 3.5 years (annualized rate 2.5% per patient-year). Patients with at least one wall irregularity had an increased risk of recurrent stroke (adjusted HR 1.4, 95% CI 1.0-1.9). There was no interaction between either randomized treatment arm (antiplatelet therapy or blood pressure control target) and wall irregularities. Irregularity by any individual artery (BA, n = 115, 14 strokes; VA, n = 150, 17 strokes; ICA, n = 268, 31 strokes; or MCA, n = 316, 37 strokes) was not predictive of recurrent stroke (each p >0.1). Conclusion: In this large well characterized cohort of lacunar stroke patients, any wall irregularity in at least one artery was associated with recurrent stroke independent of clinical risk factors and assigned treatment groups.