Sequential laser therapy of twin-twin transfusion syndrome (TTTS) includes laser obliteration of arteriovenous (AV) anastomoses from donor to recipient (AVDR) before obliterating AV anastomoses from recipient to donor (AVRD). This strategy allows for a beneficial intra-operative transfusion of blood from the hypervolemic recipient to the hypovolemic donor. In the present study, we sought to analyze the benefits and risks of sequential laser therapy with our computational model to aid its more widespread introduction. We simulated an equally shared placenta with an AVDR and a smaller diameter AVRD causing TTTS at 20 weeks. Laser coagulation and various volumes and directions of inter-twin transfusion were simulated at 21 weeks. A typical result is that when an AVDR is coagulated first, and 10 min later the AVRD with inner diameter of about 1 mm, an inter-twin transfusion of 25 ml may result from the recipient to the donor, based on literature data of AV flow versus diameter. This procedure causes a simulated loss of 50% of the recipient's blood volume. The opposite coagulation sequence, thus coagulating the AVRD first, 10 min later followed by the AVDR of 1 mm inner diameter, causes a loss of the donor's blood volume of 64%. In conclusion, our simulations support the concept of sequential laser therapy for TTTS and suggest directions for an improved safety and efficacy of this strategy.