Endoscopic Nd:YAG laser coagulation of superficial chorionic plate vessels has been suggested as a 'causal' therapy for severe twin-to-twin transfusion syndrome (TTS), as it is believed to arrest flow over vascular anastomoses. The therapy remains debated, partly because it is questioned whether coagulation of superficial chorionic vessels can arrest blood flow over deeply located anastomoses. The latter are believed to be responsible for the majority of cases of severe TTs. In this study, the coagulation performance, and the immediate and delayed tissue effects of laser coagulation were evaluated in an in vivo ovine model. Eight pregnant ewes of about 100 days' gestational age (term= 145 days) were studied. In utero coagulation was done through a 1.2 mm fetoscope loaded with a 600 microm laser fibre, connected to an Nd:YAG laser in continuous mode. Superficial cotyledonary vessels were coagulated under visual control at a distance of 1 cm with a mean power of 60 watts. 31 lasered cotyledons were harvested, either immediately (n= 15), 14 days (n = 8) or 42 days (n = 8) after the surgery and evaluated by inspection and histology. Control cotyledons were either neighbouring cotyledons from the same amniotic sac (internal control) or cotyledons from another gestational-age-matched sac (external control). Immediate effects consisted of localized coagulation necrosis at the zone of laser impact with no significant histological effect at more than 2 mm distance, except tissue congestion. Long-term effects consisted of fibrosis without any vascular recanalization or tissue regeneration extending from the impact site over the whole cotyledon. All treated cotyledons underwent complete infarction over time. This study provides experimental evidence supporting that laser coagulation of superficial chorionic vessels entering a cotyledon achieves complete functional elimination of the involved cotyledon.