Nephrolithiasis has been identified in managed populations of bottlenose dolphins (Tursiops truncatus); most of these nephroliths are composed of 100% ammonium acid urate (AAU). Several therapies are being investigated to treat and prevent nephrolithiasis in dolphins including the alkalization of urine for dissolution of nephroliths. This study evaluates the solubility of AAU nephroliths in a phosphate buffer, pH range 6.0–8.0, and in a carbonate–bicarbonate buffer, pH range 9.0–10.8. AAU nephroliths were obtained from six dolphins and solubility studies were conducted using reverse-phase high performance liquid chromatography with ultraviolet detection at 290 nm. AAU nephroliths were much more soluble in a carbonate–bicarbonate buffer, pH range 9.0–10.8 compared to phosphate buffer pH range 6.0–8.0. In the pH range 6.0–8.0, the solubility was 45% lower in potassium phosphate buffer compared to sodium phosphate buffer. When citrate was used along with phosphate in the same pH range, the solubility was improved by 13%. At pH 7 and pH 8, 150 mM ionic strength buffer was optimum for dissolution. In summary, adjustment of urinary pH alone does not appear to be a useful way to treat AAU stones in bottlenose dolphins. Better understanding of the pathophysiology of AAU nephrolithiasis in dolphins is needed to optimize kidney stone prevention and treatment.