Background and objectives: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited progressive disorder associated with significant pain and discomfort affecting quality of life. This study determined the impact of pain medication use and other clinical, biochemical and genetic characteristics on the physical and mental well being of predialysis ADPKD patients using the Short Form 36 (SF-36) questionnaire. Design, setting, participants, & measurements: The authors prospectively evaluated ADPKD patients in the Cohort Study, funded by the Polycystic Kidney Disease Foundation. Data on clinical, biochemical, and radiologic variables were collected in patients who were given the Short Form-36 questionnaire. Variables independently associated with the Physical Component Summary (PCS) and the Mental Component Summary (MCS) scores were identified. Results: One hundred fifty-two patients had a mean PCS and MCS of 46.9 ± 11.3 and 51.0 ± 9.0, similar to the general population and better than the ESRD population. Eleven (7%) reported pain medication intake within 1 mo of evaluation and demonstrated lower PCS than those not taking pain medications. Patients with GFR ≥ 80 ml/min/1.73 m2 had greater PCS than those with GFR < 80 ml/min/1.73 m2. Age, BMI, pulse pressure, pain medication use, and education level independently associate with PCS and account for 32% of the variability of the measurement. Pulse pressure correlated with MCS. Conclusions: Predialysis ADPKD patients assess their quality of life similar to the general population. Age, BMI, pulse pressure, pain medication intake, and education level link to their physical well-being. Copyright © 2009 by the American Society of Nephrology.