Surgical site infections (SSIs) contribute to morbidity and are costly to the healthcare system. To identify factors associated with SSIs. Case-control study analyzing the Nationwide Readmission Database (NRD). We identified 45,445 SSIs. Infection rates were higher in those who were obese (BMI ≥ 30) (OR: 1.39, 95% CI 1.28-1.51), tobacco users (OR: 1.08, 95% CI 1.02-1.15), diagnosed with diabetes (OR: 1.16, 95% CI 1.10-1.22), with Elixhauser Comorbidity Index ≥ 2 (OR: 1.14, 95% CI 1.09-1.20), admitted to hospital for 4-6days (OR: 1.35, 95% CI 1.29-1.42), in medium-size hospital (OR: 1.15, 95% CI 1.05-1.26), or large-size hospital (OR: 1.43, 95% CI 1.31-1.56). In contrast, patients who were 60-79years old (OR: 0.78, 95% CI 0.73-0.84), 80years or older (OR: 0.66, 95% CI 0.59-0.73), female (OR: 0.95, 95% CI 0.91-0.99), underweight (BMI < 18.5) (OR: 0.14, 95% CI 0.03-0.59), in a non-metropolitan hospital (OR: 0.83, 95% CI 0.75-0.91), self-pay (OR: 0.82, 95% CI 0.74-0.91), or covered by Medicare (OR: 0.86, 95% CI 0.80-0.91) had lower odds. Initial data entry to NRD is susceptible to human error. Patients who are obese, use tobacco, have multiple comorbidities, and have long hospital stays in medium-to-large-size hospitals are at risk of SSIs. Conversely, odds of SSIs are lower in females, age ≥ 60, BMI < 18.5, self-pay or Medicare (versus private insurance), or at smaller hospitals. Understanding factors associated with SSIs may help surgeons anticipate complications.