We aimed to investigate the prognostic factors for, and treatment efficacy of, intense pulsed light (IPL) treatment with a vascular filter in patients with moderate or severe meibomian gland dysfunction (MGD). In this retrospective observational study, 58 moderate or severe MGD patients who underwent IPL treatment with a vascular filter were enrolled. IPL treatment was administered to the upper and lower eyelids four times at two-week intervals. At baseline, and four weeks after IPL, we evaluated the matrix metalloproteinase (MMP)-9 expression levels, tear break-up times (TBUT), ocular surface staining scores, lid margin telangiectasias, and meibomian gland characteristics. The subjective symptoms and adverse effects were reviewed and recorded. Regression analyses were performed to explore the prognostic factors affecting clinical outcomes. IPL treatment using a vascular filter led to improvements in the TBUT, ocular surface staining score, meibomian gland grade, meibum quality and consistency, lid margin telangiectasia, and symptom score (all p < 0.001). Furthermore, the positivity rate (90.2% to 70.6%, p = 0.013) and expression levels (1.92 ± 1.18 to 1.24 ± 1.18, p < 0.001) of tear MMP-9 improved after the IPL treatment. In multivariate logistic regression analysis, a young age (odds ratio = 0.867, p = 0.007) and a toothpaste-like consistency in the upper lid (odds ratio = 8.449, p = 0.046) were associated with improvements in the meibomian gland grade. No adverse effects were detected. IPL with a vascular filter is a safe and effective treatment for moderate and severe MGD. Age and the meibum consistency in the upper lid are important prognostic factors.