OBJECTIVES:  To estimate the infection rate and the annual health expenditures associated with spinal cord stimulation (SCS)-related infection. METHODS: Data from the Truven MarketScan® Commercial Claims and Medicare Supplemental databases were used to identify patients with a SCS neurostimulator generator implant during the calendar years 2009–2014. Patients were continuously enrolled for at least 12 months before and after implant. The patients were further divided into initial group or replacement group. Annual expenditures were estimated for patients who experienced a device-related infection versus those without infection since SCS generator implant. The generalized linear model was conducted to estimate annual expenditures, utilizing a gamma distribution and a log link function. All multivariable expenditure models were conducted separately for patients in the initial group and the replacement group. All models were controlled for presence of infection before generator implant, Charlson comorbidity index score, as well as patient demographics. RESULTS: The study included 6,615 patients: 5,563 patients were identified as the initial group, and 1,052 patients were identified as the replacement group. The overall SCS-related infection rate within 12-months post-implant was 3.11%. The infection rates for the initial group (3.09%) and replacement group (3.23%) were not significantly different (p=0.8104). The multivariable expenditure models revealed that patients with infection had higher annual expenditures than patients without infection in both initial implant and replacement implant groups. Estimated incremental annual healthcare expenditures for patients with an infection were $59,716 (95% CI: $48,965-$69,480) for initial implanted patients and $64,833 (95% CI: $37,377 - 86,519) for replacement patients. CONCLUSIONS:  The approximate 3% infection rate within 12-months of SCS implant determined from a large administrative database further emphasizes the need for improvement in SCS infection control practices. The result shows the expenditure burden associated with SCS-related infection is substantial, and the management of SCS-related infection is important from both clinical and economic standpoints.