Objective The low welding strength of laser-assisted vascular anastomosis (LAVA) has hampered the clinical application of LAVA as an alternative to suture anastomosis. To improve welding strength, LAVA in combination with solder and polymeric scaffolds (ssLAVA) has been optimized in vitro. Currently, ssLAVA requires proof-of-concept in a physiologically representative ex vivo model before advancing to in vivo studies. This study therefore investigated the feasibility of ex vivo ssLAVA in medium-sized porcine arteries. Methods Scaffolds composed of poly(e-caprolactone) (PCL) or poly(lactic-co-glycolic acid) (PLGA) were impregnated with semisolid solder and placed over coapted aortic segments. ssLAVA was performed with a 670-nm diode laser. In the first substudy, the optimum number of laser spots was determined by bursting pressure analysis. The second substudy investigated the resilience of the welds in a Langendorf-type pulsatile pressure setup, monitoring the number of failed vessels. The type of failure (cohesive vs adhesive) was confirmed by electron microscopy, and thermal damage was assessed histologically. The third substudy compared breaking strength of aortic repairs made with PLGA and semisolid genipin solder (ssLAVR) to repairs made with BioGlue. Results ssLAVA with 11 lasing spots and PLGA scaffold yielded the highest bursting pressure (923 ± 56 mm Hg vs 703 ± 96 mm Hg with PCL ssLAVA; P = .0002) and exhibited the fewest failures (20% vs 70% for PCL ssLAVA; P = .0218). The two failed PLGA ssLAVA arteries leaked at 19 and 22 hours, whereas the seven failed PCL ssLAVA arteries burst between 12 and 23 hours. PLGA anastomoses broke adhesively, whereas PCL welds failed cohesively. Both modalities exhibited full-thickness thermal damage. Repairs with PLGA scaffold yielded higher breaking strength than BioGlue repairs (323 ± 28 N/cm2 vs 25 ± 4 N/cm2, respectively; P = .0003). Conclusions PLGA ssLAVA yields greater anastomotic strength and fewer anastomotic failures than PCL ssLAVA. Aortic repairs with BioGlue were inferior to those produced with PLGA ssLAVR. The results demonstrate the feasibility of ssLAVA/R as an alternative method to suture anastomosis or tissue sealant. Further studies should focus on reducing thermal damage.