Surgical site infections (SSI) after vascular surgery are related to substantial morbidity. Restriction of bacterial access to the site of surgery with a cyanoacrylate sealant is a new concept. We performed a randomized clinical trial to assess the effect of the sealing of skin with a cyanoacrylate preparation at the site of surgery on the incidence of SSI after arterial reconstruction. Methods: Patients scheduled for vascular reconstruction in or distal to the groin were randomized into a treatment and a control group. Standard measures for preventing contamination of the surgical field were taken in the control group, whereas cyanoacrylate was used as a skin sealant at the surgical site in the patients in the treatment group. We hypothesized that the incidence of SSI with the use of cyanoacrylate would be two-thirds (67%) lower than that with standard preparation of the surgical site, and performed an interim analysis of 50 patients to assess this. Results: Risk factors among the 50 patients in the study included smoking (28%), hypertension (77%), diabetes mellitus (36%), and hypercholesterolemia (74%). Indications for surgery were invalidating claudication (Fontaine IIb), pain at rest, or tissue necrosis. The overall incidence of SSI was 3/47 (6%), without differences between groups; 9% SSIs in the control group versus 4% SSIs in the intervention group. Conclusion: We could not confirm a reduction in the incidence of SSI after inguinal vascular surgery with the use of a cyanoacrylate skin sealant as compared with conventional means for preparing the surgical site.