Abstract Background Restenosis driven by intimal hyperplasia remains a major limitation of peripheral arterial intervention. Photodynamic therapy (PDT) using porfimer sodium (Photofrin®) demonstrated promising preclinical efficacy in the 1990s; however, its translation into clinical vascular practice has stalled. We reappraised a historical pilot dataset to evaluate both the biological efficacy and procedural feasibility. Methods In a rabbit model of bilateral femoral artery balloon injury (10 animals initiated), one artery per animal received intraluminal PDT (630 nm, ~5.6 J/cm²) 48 h after intramuscular porfimer sodium administration (2 mg/kg), while the contralateral artery served as an internal control. Histomorphometric analysis of the intima–media ratio (IMR) was performed 21 days after the injury. Results The procedural feasibility was severely limited. Only three of the ten animals yielded analyzable paired arterial samples due to high intraoperative mortality (40%) and postoperative complications. In surviving animals, PDT-treated arteries demonstrated a consistent and marked suppression of neointimal hyperplasia compared with controls (IMR 0.29 ± 0.07 vs. 1.65 ± 0.55; P < 0.001), corresponding to a median IMR reduction of 82%. Conclusions This reappraisal confirms the potent biological effects of porfimer sodium–mediated PDT on neointimal hyperplasia. However, the principal contribution of this study lies in the transparent documentation of critical translational barriers, particularly the unsustainable procedural mortality associated with this bilateral injury model. By providing detailed dosimetry parameters and a candid feasibility analysis, this study offers methodological insights to guide the design of safer and more translatable preclinical vascular PDT studies.