The use of subatmospheric pressure to promote wound healing has increased in popularity during the last several years. The original studies on granulation tissue formation used a 125-mmHg vacuum. The use of alternative sources of subatmospheric pressure has led to many questions regarding efficacy or risk. In this report a swine model is used to quantify and compare the effects of low vacuum suction (25 mmHg) and high vacuum suction (500 mmHg) produced by various vacuum pumps and wall suction systems with the standard 125-mmHg vacuum. Additionally, the effects of an unregulated air leak in the sealing system were examined. All four wound treatments were examined on each of 4 pigs. Wounds were treated until one of the wounds had granulated to a level flush with the surrounding tissue. Wounds treated with the standard 125-mmHg vacuum had filled with granulation tissue by day 8. At this time wounds treated with 25 mmHg had filled 21.2% with new granulation tissue, and wounds treated with 500 mmHg had filled 5.9% with new tissue. Wounds treated with 125 mmHg with a hole in the sealing drape had increased in size 197% because of the debridement of necrotic tissue. In conclusion, wounds treated with a 125-mmHg vacuum exhibited a significant (p < 0.0001) increase in the rate of granulation tissue formation compared with treatment at 25 mmHg or 500 mmHg. The presence of an unregulated air leak in the sealing drape results in significant progression (p < 0.0001) of the wound secondary to dehydration and progressive necrosis.