Background The incidence of organ-space surgical site infections (OSIs) across the US has not decreased to the same extent as superficial and deep surgical site infections (SSIs). This study aimed to highlight the consequences and create a predictive model of OSIs using 2019 NSQIP data. Materials and Methods The primary data source was the ACS NSQIP 2019 Participant Use Targeted File (PUF). Chi-squared and independent t-tests evaluated the association of OSIs and other postoperative complications. Variables of interest for our predictive model included 10 surgery types, 10 relevant preoperative laboratory values, and 26 other variables including demographics and comorbidities. A stepwise logistic regression model fit with OSIs as the outcome was used to calculate the predicted ROC and c-index. Results A total of 1,076,441 cases submitted from 719 NSQIP-participating sites were included in our analysis, comprised of 16,751 (1.6%) OSIs with a median of 10 days (IQR: 11 days) between surgery and the development of an OSI. Forty-two variables were included in our final multivariable analysis. Esophageal and pancreatic surgeries yielded an approximate 4- and 6-fold higher increase in the odds of OSI, respectively ( P < .001). ROC analysis yielded a c-index statistic of 0.846 ( Figure 1 ). Associated consequences of OSIs included hospital readmission (OR = 20.74, 95% CI: 20.094-21.412, p < .001), sepsis (OR = 35.084; 95%CI: 33.75-36.47, p < .001) and higher probabilities of mortality (34% vs. 0.8%, p < .001) and morbidity (16% vs. 5.8%, p < .001). Discussion OSIs have extensive consequences and may be predictable. These types of infections are multifactorial and require quality surveillance distinct from other SSIs.