Hydrochlorothiazide (1 mg/kg PO q12h) or placebo was administered to healthy cats for 2 weeks in a masked, placebo-controlled, crossover-design study, and 24-hour urine samples were collected. When cats received hydrochlorothiazide, 24-hour urine volume, ammonia, chloride, creatinine, magnesium, oxalic acid, phosphate, potassium, and sodium were significantly higher than when cats received placebo. Hydrochlorothiazide was associated with significantly lower urinary saturation for calcium oxalate, but no difference was found in 24-hour urine calcium and citrate, urinary saturation for struvite, or blood ionized calcium. Hydrochlorothiazide decreased urinary saturation for calcium oxalate and could be useful in managing cats with calcium oxalate uroliths. Results of this study, however, should not be extrapolated to cats that form calcium oxalate uroliths.