Single-vessel vs multivessel revascularization for critical limb ischemia (CLI) remains controversial. The purpose of this study was to evaluate single vs multiple tibial vessel interventions in patients with multivessel tibial disease. Using the Vascular Quality Initiative registry, we reviewed patients undergoing lower extremity endovascular interventions involving the tibial arteries. Patients with CLI were included if at least two tibial vessels were diseased and appropriate follow-up was documented. Primary outcomes were amputation, primary assisted patency, and amputation-free survival (AFS). After exclusions, a total of 761 patients with multivessel tibial disease and CLI were evaluated. Of these, 473 (62.1%) underwent single-vessel tibial intervention (group 1), whereas 288 (37.9%) underwent multivessel (two or more) intervention (group 2). Patients in group 2 were younger (69.1 vs 73.2 years; P < .001), with higher chance of smoking (29.5% vs 18.2%; P < .001). Prior ipsilateral amputation (19.2% vs 22.2%; P = .22) or inflow procedures (3.1% vs 2.8%; P = .29) were similar. Group 1 more commonly had concurrent femoral or popliteal inflow interventions (83.7% vs 78.1%; P = .05). Multivessel runoff on completion was significantly greater for group 2 (99.9% vs 39.9%; P < .001). Mean follow-up was 337 ± 62 days. No differences were observed between group 1 and group 2 for major amputation (9.0% and 7.6%; P = .6), patency (89.7% vs 86.8%; P = .45), or AFS (P = .372; Fig). In a multivariate Cox model, loss of patency was the only significant predictor of major amputation (hazard ratio, 5.36 [2.7-10.6]; P = .01). A subgroup analysis of 355 (46.6%) patients with tissue loss data showed that tissue loss before intervention was not predictive of future major amputation. In the Vascular Quality Initiative registry, patients with CLI and multivessel tibial disease did not appear to benefit in amputation, AFS, or primary assisted patency when undergoing multivessel tibial intervention compared with single tibial revascularization. Further studies are needed to determine when multivessel treatment is warranted for this population.