OBJECTIVES Chemotherapy-associated peripheral neuropathy (CAPN) is a painful side-effect of chemotherapy. Comprehensive measures of health outcomes, medical costs, and workloss burden of CAPN in patients with breast, ovarian, head/neck, or non-small cell lung cancer (NSCLC) have not been quantified. This study assesses the outcomes and direct and indirect cost burden of CAPN in these four tumor types from a third-party payer perspective. METHODS Data were from an administrative claims database of privately insured companies covering 1999-2006. Patients with qualifying tumors, and claims for chemotherapy and services indicative of peripheral neuropathy (PN) within 9-months of chemotherapy were selected. Cases were matched 1:1 to controls with no PN-related claims based on cancer type, diabetes history, demographics, and propensity for reporting PN claims during the study period (estimated on baseline resource use and comorbidities). Direct costs and resource use were calculated for a 12-month study period using diagnosis and procedure codes, pharmacy claims, and provider specialty codes. Indirect costs were obtained for a subset of patients that had disability and medically related absenteeism data. Comparisons of cost and resource use between cases and controls used paired t-tests. RESULTS Among patients treated for breast, ovarian, head/neck, and NSCLC, 454 were identified who met inclusion criteria and had evidence of CAPN. Average direct costs were $17,344 higher for CAPN cases than non-CAPN controls (p<0.0001). Outpatient costs were the highest component for both cases and controls with cases having excess outpatient costs of $8092 (p<0.001). On average, each CAPN case had 12 more outpatient visits than controls (51.3 vs. 39.8 visits; p<0.0001), and spent more days in the hospital (5.6 vs. 3.2 days; p<0.001). Indirect resource use and costs were higher for cases but not statistically different from controls. CONCLUSIONS CAPN is associated with increased direct medical cost and resource use of patients with breast, ovarian, head/neck, or NSCLC.