PURPOSE: Potassium citrate therapy has become one of the cornerstones of medical stone management. We elucidated the long-term effects of potassium citrate on urinary metabolic profiles and its impact on stone formation rates. MATERIALS AND METHODS: We performed a retrospective cohort study in patients treated at the Comprehensive Kidney Stone Center at our institution between 2000 and 2006. Patients with pre-therapy and post-therapy 24-hour urinary profiles available who remained on potassium citrate for at least 6 months were included in the analysis. RESULTS: Of the 1,480 patients with 24-hour urinary profiles 503 met study inclusion criteria. Mean therapy duration was 41 months (range 6 to 168). Overall a significant and durable change in urinary metabolic profiles was noted as soon as 6 months after the onset of therapy. These changes included increased urinary pH (5.90 to 6.46, p <0.0001) and increased urinary citrate (470 to 700 mg a day, p <0.0001). The stone formation rate also significantly decreased after the initiation of potassium citrate from 1.89 to 0.46 stones per year (p <0.0001). There was a 68% remission rate and a 93% decrease in the stone formation rate. CONCLUSIONS: Potassium citrate provides a significant alkali and citraturic response during short-term and long-term therapy with the change in urinary metabolic profiles sustained as long as 14 years of treatment. Moreover, long-term potassium citrate significantly decreases the stone formation rate, confirming its usefulness in patients with recurrent nephrolithiasis.