Objectives: To validate a health-related quality-of-life (QOL) instrument for patients following neck dissection and to identify the factors that affect QOL following neck dissection. Design: Cross-sectional validation study. Setting: The outpatient clinic of a tertiary care cancer center. Patients: Convenience sample of 54 patients previously treated for head and neck cancer who underwent a selective neck dissection or modified radical neck dissection (64 total neck dissections). Patients had a minimum postoperative convalescence of 11 months. Thirty-two underwent accessory nerve-sparing modified radical neck dissection, and 32 underwent selective neck dissection. Main Outcome Measure: A 10-item, self-report instrument, the Neck Dissection Impairment Index (NDII), was developed and validated. Reliability was evaluated with test-retest correlation and internal consistency was assessed using the 36-Item Short-Form. Health Survey (SF-36) and the Constant Shoulder Scale, a shoulder function test. Multiple variable regression was used to determine variables that most affected QOL following neck dissection Results: The 10-item NDII test-retest correlation was 0.91 (P<.001) with an internal consistency Cronbach α coefficient of .95. The NDII correlated with the Constant Shoulder Scale (r=0.85, P<.001) and with the SF-36 physical functioning (r=0.50, P<.001) and role-physical functioning (r=0.60, P<.001) domains. Using multiple variable regression, the variables that contributed most to QOL score were patient's age and weight, radiation treatment, and neck dissection type. Conclusions: The NDII is a valid, reliable instrument for assessing neck dissection impairment. Patient's age, weight, radiation treatment, and neck dissection type were important factors that affect QOL following neck dissection.