Maintaining a vacuum when applying negative pressure wound therapy (NPWT) is the key to its function, which is a challenge in the perineum, buttocks, and sacrococcygeal region. A retrospective cohort study was conducted to assess the effect of hydrocolloid dressings on preventing air leakage when applying NPWT in these regions. There were 61 patients in Group A (without the aid of hydrocolloid dressings) and 65 patients in Group B (with the aid of hydrocolloid dressings). The hydrocolloid dressing-assisted NPWT significantly reduced the incidence of air leakage compared with conventional NPWT placement (24.6% vs. 7.7%; risk ratio, 3.20; 95% confidence interval, 1.24–8.27; p = 0.009), while decreasing the number of open NPWT applications (2.2 vs. 1.7; difference, 0.43; 95% confidence interval, 0.19–0.66; p < 0.001), shortening hospital stays (20.1 vs. 16.1; difference, 4.07; 95% confidence interval, 1.68–6.46; p = 0.01), and reducing the incidence of adverse skin events (18.0% vs. 4.6%; risk ratio, 3.91; 95% confidence interval, 1.14–13.34; p = 0.017). These findings support the routine use of hydrocolloid dressing-assisted NPWT placement in the perineum, buttocks, and sacrococcygeal region.