Aim Drug-coated balloon (DCB) angioplasty is a common endovascular treatment that has lower rates of restenosis compared to plain angioplasty. Restenosis rates remain higher than is desirable even with the use of DCB technology. This study was undertaken to investigate whether guidance using IVUS resulted in lower rates of restenosis. Methods A subgroup of patients who undergone primary treatment with DCB and had one year follow-up available was extracted from cases enrolled in an on-going RCT investigating the use of IVUS guidance in femoropopliteal endovascular interventions. Patient, lesion and procedural parameters were compared between the treatment group (who had IVUS and angiographic guidance) and the control group (only angiography guidance). The rate of binary restenosis was compared between the two groups. Results A total of 76 patients had treatment by DCB (36 in control group and 40 in treatment group). There was no difference in parameters between the two groups. There was a significantly higher rate of binary restenosis at one year in the control group compared to the treatment group (47% v 15%, p=0.003). Median balloon size was significantly larger in the treatment group than the control group (6 mm v 5 mm, p=0.019). The median difference between the angiographic measurement and the actual treated length was significantly greater in the treatment group compared to the control group (40 v. 0 mm), p=0.010. Conclusion These findings suggest that the reduced rate of restenosis rates found when IVUS guidance was used may be due to optimised drug delivery during DCB treatment by improved matching of the DCB to the vessel lumen dimensions and better coverage of the true lesion length.