OBJECTIVE:: To assess the overall burden of healthcare-associated infections (HAIs) in patients exposed and nonexposed to surgery. BACKGROUND:: Targeted HAI surveillance is common in healthcare institutions, but may underestimate the overall burden of disease. METHODS:: Prevalence study among patients hospitalized in 50 acute care hospitals participating in the Swiss Nosocomial Infection Prevalence surveillance program. RESULTS:: Of 8273 patients, 3377 (40.8%) had recent surgery. Overall, HAI was present in 358 (10.6%) patients exposed to surgery, but only in 206 (4.2%) of 4896 nonexposed (P < 0.001). Prevalence of surgical site infection (SSI) was 5.4%. Healthcare-associated infections prevalence excluding SSI was 6.5% in patients with surgery and 4.7% in those without (P < 0.0001). Patients exposed to surgery carried less intrinsic risk factors for infection (age >60 years, 55.6% vs 63.0%; American Society of Anesthesiologists score >3, 5.9% vs 9.3%; McCabe for rapidly fatal disease, 3.9% vs 6.6%; Charlson comorbidity index >2, 12.3% vs 20.9%, respectively; all P < 0.001) than those nonexposed, but more extrinsic risk factors (urinary catheters, 39.6% vs 14.1%; central venous catheters, 17.8% vs 7.1%; mechanical ventilation, 4.7% vs 1.3%; intensive care stay, 18.3% vs 8.8%, respectively; all P < 0.001). Exposure to surgery independently predicted an increased risk of HAI (odds ratio 2.43; 95% CI 2.0-3.0). CONCLUSIONS:: Despite a lower intrinsic risk, patients exposed to surgery carried more than twice the overall HAI burden than those nonexposed; almost half was accountable to SSI. Extending infection control efforts beyond SSI prevention in these patients might be rewarding, especially because of the extrinsic nature of risk factors.