Following non-anatomical resection of lung parenchyma with a Nd:YAG laser, a coagulated surface remains. As ventilation starts, air leakage may occur in this area. The aim of the present study was to investigate, whether additional coagulation either before or after ventilation has an additional sealing effect. Freshly slaughtered porcine heart-lung blocks were prepared. The trachea was connected to a ventilator. Using a Nd:YAG laser (wavelength: 1320 nm, power: 60 W), round lesions (1.5 cm in diameter) with a depth of 1.5 cm were applied to the lung using an 800-μm laser fiber (5 s per lesion). Group 1 (n = 12) was control. Additional coagulation was performed in group 2 (n = 12) without and in group 3 (n = 12) with ventilation restarted. Air leakage (ml) from the lesions was measured. The thickness of each coagulation layer was determined on histological slices. Differences between individual groups were analyzed by one-way ANOVA (significance p < 0.05). After resection, 26.2 ± 2.7 ml of air emerged from the lesions per single respiration in group 1. Air loss in group 2 was 24.6 ± 2.5 ml (p = 0.07) and in group 3 23.7 ± 1.8 ml (p = 0.0098). In comparison to groups 1 and 2 thickness of the coagulation layers in group 3 was significantly increased. After non-anatomical porcine lung resection with a Nd:YAG laser, additional coagulation of the ventilated resection area can reduce air leakage.