The clinical role for pentosan polysulfate (PPS) in the prevention of calcium oxalate urolithiasis is not known. Crystallization and aggregation are important steps in calcium oxalate stone formation, and PPS has been shown to inhibit these steps, both in vitro and in vivo. In addition, PPS has a role in repairing injured urothelium and inhibiting adhesion to epithelial defects. A randomized double-blind placebo-controlled study appears warranted to assess the utility of PPS in the prevention of recurrent calcium oxalate stones.