Purpose The relationship between atherosclerosis and total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), Lipoprotein(a) (Lp(a)), triglyceride (TG), and homocysteine level is well established. Few studies have examined the relationship between these serum biomarkers and long-term stent patency, following endovascular stenting of aorto-iliac occlusive disease (AIOD). Methodology We report a retrospective post-hoc analysis of the Covered versus Balloon Expandable Stent Trial (COBEST) at Royal Perth Hospital and other Australian COBEST centres. Patients were observed for five-years following endovascular stenting. Primary endpoint was stent patency, as determined by ultrasound imaging or angiography. Stent patency was compared with TC, HDL, LDL, Lp(a), TG and homocysteine. Results Aorto-iliac stents were placed in 168 patients (83 covered stents and 85 bare metal stents). Baseline characteristics were similar between the two groups. The cohort was primarily Caucasian (97%). There was no significant difference in the distribution of the biomarkers between the two groups. Covered stents had significantly higher patency than bare-metal stents in Trans-Atlantic Inter-Society Consensus C and D lesions (Hazard ratio [HR], 8.639, 95% CI, 54.253–75.753; P < 0.001). Patency of stents at five years was markedly reduced in patients with Lp(a) elevated above the normal range (HR: 10.38, 95%CI 5.39–19.99, P<0.001); elevated TG (HR: 5.92, 95%CI 3.37–10.38, P<0.001); elevated homocysteine level (HR: 5.21, 95%CI 2.70–10.07, P<0.001), and an elevated LDL ratio (HR: 6.14, 95%CI 2.70–11.41, P<0.001). Conclusion Following endovascular stenting of aorto-iliac disease, stent patency at five-years is markedly reduced in patients with increased Lp(a), TG, homocysteine, and LDL ratio. This may impact patient selection and counselling; and raises the hypothesis that aggressive post-procedural treatment of biomarkers may improve long-term outcomes.