Introduction and objective: Postoperative infections are a great constituent of surgical complications. The most common one is surgical site infection (SSI), as well as vaginal and/or urinary tract infections, infections affecting distant organs and systems and systemic circulation leading to sepsis and septic shock. Our aim was to emphasize the effect of malignant disease on postoperative infection and to establish malignant disease as a risk factor for SSI, per se. Material and Method: We designed a retrospective study in which 538 women who underwent surgery in the Gynecology and Obstetrics Clinical Center of Serbia during a six-month period in 2009 were analyzed. We collected relevant data regarding SSI incidence (CDC definitions), malignant disease (primary site, type and stage) and other potential risk factors for SSI. We used descriptive statistics, chi-square and Student’s t test for comparison of variables with statistical significance at p < 0.05. We also used univariate, multivariate logistic regression and ROC analysis. Results: Surgical site infection was present in 40 patients (7.5%). Univariate analysis revealed that the following factors were significantly related to SSI: age, malignant disease, stage of malignant disease, surgery longer than 120 min, postmenopause, diabetes mellitus, positive preoperative vaginal culture, ASA score and intraoperative blood loss. Multivariate analysis showed that the most important risk factors that contribute to SSI with RR of 4 and 5 are, respectively, FIGO II and FIGO III/IV stage of malignant disease (FIGO II p < 0.05 RR= 4.097; FIGO III/IV < 0.01 RR = 5.061). Conclusion: In our study malignant disease erupted as the most important risk factor for SSI. This brings us to question the pathophysiological mechanisms and systemic effects associated with malignant disease. There are few studies discussing the issue of malignancy as an isolated risk factor that 4-5 fold increases the risk of SSIs. It is of utmost interest to define protocols of antimicrobial prophylaxis for gynecological malignancy surgery as are suggested for some other malignancies.