Objective. Inadequate prescription therapy pain management, lack of doctor-patient communication about over-the-counter (OTC) medications, and easy accessibility of OTC medications may contribute to patients using more than 1 medication to manage pain. It is well established that taking multiple nonsteroidal antiinflammatory drugs (NSAIDs) can lead to serious gastrointestinal problems. Little is known about whether use of more than 1 NSAID (i.e., dual use) is related to patient self-reported outcomes, specifically health-related quality of life (HRQOL). We hypothesized that dual use of NSAIDs would be associated with reduced HRQOL. Methods. Patients from a managed care organization who filled ≥1 NSAID prescription over a 6-month period were eligible for a telephone interview focusing on NSAID use, which included the Short Form 12 (SF-12) Health Survey. Dual use was defined as taking 2 NSAIDs, either prescription or OTC, at least twice weekly during the past month. A multivariable linear regression model examined the association between dual use and the Physical Component Summary score (PCS-12) from the SF-12. Results. Dual use was associated with lower PCS-12 scores indicating poorer HRQOL, after controlling for clinical and demographic factors. Conclusion. Patients may self-manage their pain to improve their daily activities by taking more than 1 NSAID. However, by attempting to obtain symptom relief, patients may be putting themselves at risk for complications. Providers are likely unaware of patients' risk. Future research should evaluate the causal factors contributing to dual use. © 2008, American College of Rheumatology.