Objective: To examine the impact of pain on functioning across multiple quality of life (QOL) domains among individuals with spinal cord injury (SCI). Design: A case-control design that matched 2 groups (i.e., extreme pain interference and no pain interference) case for case on age (i.e., within 10 years), education, gender, race, marital status, primary occupation, and impairment level. Etiology of SCI and injury duration, although not specifically matched, were the same in 84% and 91% of the cases, respectively. Participants: Individuals with traumatic-onset SCI from the National Spinal Cord Injury database (n = 86 matched pairs). Outcome Measures: Satisfaction With Life Scale, Craig Handicap Assessment and Reporting Technique, and Short Form SF-12. Results: The extreme pain interference group reported a significantly lower overall QOL and had higher total handicap scores than the no pain interference group. Areas of handicap most influenced by pain were mobility, social integration, and economic self-sufficiency. The extreme pain interference group also reported significantly lower physical and mental health than the no pain interference group. Conclusions: Pain has a consistent detrimental impact on functioning across multiple QOL domains even after controlling for multiple demographic and medical characteristics known to be associated with self-reported QOL.