Background and objectives: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by increased total kidney volume (TKV) and renal failure. This study aimed to determine if height-adjusted TKV (htTKV) predicts the onset of renal insufficiency. Design, setting, participants, & measurements: This prospective, observational, longitudinal, multicenter study included 241 adults with ADPKD and preserved renal function. Magnetic resonance imaging and iothalamate clearance were used to measure htTKV and GFR, respectively. The association between baseline htTKV and the attainment of stage 3 CKD (GFR<60 ml/min per 1.73 m 2) during follow-up was determined. Results: After a mean follow-up of 7.9 years, stage 3 CKD was attained in 30.7% of the enrollees. Using baseline htTKV, negative correlations with GFR increased from -0.22 at baseline to -0.65 at year 8. In multivariable analysis, a baseline htTKV increase of 100 cc/m significantly predicted the development of CKD within 8 years with an odds ratio of 1.48 (95% confidence interval: 1.29, 1.70). In receiver operator characteristic curve analysis, baseline htTKV of 600 cc/m most accurately defined the risk of developing stage 3 CKD within 8 years with an area under the curve of 0.84 (95% confidence interval: 0.79, 0.90). htTKVwas a better predictor than baseline age, serum creatinine, BUN, urinary albumin, or monocyte chemotactic protein-1 excretion (P<0.05). Conclusions: Baseline htTKV ≥600 cc/m predicted the risk of developing renal insufficiency in ADPKD patients at high risk for renal disease progressionwithin 8 years of follow-up, qualifying htTKV as a prognostic biomarker in ADPKD. © 2012 by the American Society of Nephrology.