Objective: This study aimed to evaluate the impacts of deep surgical site infections (dSSIs) regarding hospital readmissions, prolonged length of stay (LoS), and estimated costs. Patients and Methods: We designed and applied a matched case–control observational study using the electronic health records at the University Medical Center Groningen in the Netherlands. We compared patients with dSSI and non-SSI, matched on the basis of having similar procedures. A prevailing topology of surgeries categorized as clean, clean-contami-nated, contaminated, and dirty was applied. Results: Out of a total of 12,285 patients, 393 dSSI were identified as cases, and 2864 patients without SSIs were selected as controls. A total of 343 dSSI patients (87%) and 2307 (81%) controls required hospital readmissions. The median LoS was 7 days (P25-P75: 2.5–14.5) for dSSI patients and 5 days (P25-P75: 1–9) for controls (p-value: <0.001). The estimated mean cost per hospital admission was €9,016 (SE±343) for dSSI patients and €5,409 (SE±120) for controls (p<0.001). Independent variables associated with dSSI were patient’s age ≥65 years (OR: 1.334; 95% CI: 1.036–1.720), the use of prophylactic antibiotics (OR: 0.424; 95% CI: 0.344–0.537), and neoplasms (OR: 2.050; 95% CI: 1.473–2.854). Conclusion: dSSI is associated with increased costs, prolonged LoS, and increased read-mission rates. Elevated risks were seen for elderly patients and those with neoplasms. Additionally, a protective effect of prophylactic antibiotics was found.