SummaryBackground: Thermal, mechano-chemical and chemical methods of vein closure are increasingly less effective in saphenous veins with diameters above 10 mm. Furthermore, increasing vein size is associated with unpleasant inflammatory reactions, in particular in locations close to sensitive structures like the skin. External compression media are not able to prevent these unwanted sequela in a tolerable way. As a possible solution, perivenous hyaluronan compression was evaluated combined with microfoam sclero-therapy.Methods: 34 patients (25 f, 9 m, 43–71 yr/o) with saphenous insufficiency (GSV), dia -meters 10.1–23.1 mm (M: 14.1 mm), distance to skin: >10 mm, received a vein lumen compression oft thigh- or calf segments by perivenous injection of a NASHA gel mediated by a coaxial paravenous catheter prior to catheter-applied microfoam sclerotherapy (aethoxysklerol 1 %). Injection of both, hyaluronan and microfoam, were performed during catheter withdrawal. The aim of hyaluronan compression was a 2/3 reduction oft the native vein cross section. For comparison, adjacent segments were compressed with common tumescent fluid. Segments for both modalities had similar diameter and were randomized. Due to department rules, the junction segment was closed with endovenous lasers to warrant elimination of reflux. No textile compression media were applied. Clinical controls including ultrasound were performed after 2, 8, 26 and 54 weeks.Results: All treated vein segments showed total occlusion after 2 weeks (first visit). The lumen reduction was 54–81 % (M: 68.4 %) in segments with hyaluronan compression and 8–29 % (M: 19.2 %) in segments with tumes-cent fluid. Time needed for hyaluronan compression was 1.1–3.5 min (M: 2.2 min) and for tumescence 0.8–2.7 min (M: 1.8 min) per 10 cm-segment. Clinical investigations up to 8 weeks did not reveal any symptoms, visible inflammations or stainings in segments covered with hyaluronan, while tumescent-compressed segments had such findings in 20/34 cases (58.8 %). Perivenous hyaluronan did not induce any discomfort or side effects during follow-up.Conclusions: Even large saphenous veins can be effectively and safely treated by microfoam sclerotherapy without any postinterventional symptoms when the vein lumen is reduced by perivenous injection of hyaluronan gel. However, it takes additional interventional effort to achieve this goal. Future applications could also include combinations with thermal or gluing device or support novel foams like Varithena or biomatrix sclerofoam when treating very large veins or venous aneurysms, and furthermore serve in vein shaping fort the purpose of establishing laminar flow or modifying pressure relations (venoplasty).