OBJECTIVES: Surgical site infections (SSIs) associated with total knee arthroplasty (TKA) have a significant negative impact on outcomes and hospital reimbursement. Our study uniquely looks at the impact of patients having SSI in their initial admission with downstream outcomes of readmission to assess the complete consequences of TKA related SSI, beyond a single episode of care. METHODS: Thomson Medstat Marketscan® Database was used to identify patients having a TKA (ICD9-CM procedure code 81.54) between January 2007 and December 2009. Patients experiencing infections were defined by ICD-9-CM codes 998.5x, 998.66 and 998.67 as their secondary diagnosis in their index admission and as their primary or secondary diagnoses during their 90-day readmissions.  Total SSI burden was assessed by evaluating differences in length of stay (LOS) and costs relative to those with no SSI in the 3 groups: 1) during the initial admission in patients developing SSI; 2) during the 90-day post surgery for patients who had developed SSI in their initial admission; and 3) in patients experiencing SSI in their postoperative period. Generalized linear models adjusting for age, gender, region and p/a diabetes were used to compute mean differences and 95% confidence intervals. RESULTS: Patients in group 1 developing SSI as a complication of TKA incur an additional LOS of 2.4 days (95%CI:2.2-2.6 days) and an extra $6360 costs (95%CI:$4610-$8100). Group 2 patients are at risk of 0.75 more downstream readmissions, and incur an average of 0.51 days additional LOS (95%CI:0.17-0.85) and $1,160 additional payments (95%CI:$130-$2180). Group 3 patients are at risk of 1.3 additional readmissions, and incur an average additional LOS of 8.2 days (95%CI:8.0-8.4) and $21,830 (95%CI:$21,160-$22,510) in additional payments. CONCLUSIONS: SSI associated with TKA increases current and downstream burden by a factor of 1.3-8.0 times in terms of readmission rates and additional LOS and provider payments.