Background: Hyperkalemia, induced by renin-angiotensin-aldosterone system inhibition (RAAS-I) in patients with chronic kidney disease (CKD), or cardiac disease often leads to withdrawal of RAAS-I therapy. Sodium polystyrene sulfonate (SPS) is a potassium-binding resin used for the treatment of hyperkalemia. Recently, concerns about the safety and efficacy of SPS were raised. We report here a follow-up of 14 patients with CKD and heart disease on RAAS-I treatment who were treated with low-dose daily SPS to prevent recurrence of hyperkalemia. Hypothesis: Daily SPS is safe and effective for secondary prevention of hyperkalemia induced by RAAS-I therapy in CKD patients with heart disease. Methods: We reviewed the medical charts of the patients with CKD (nondialysis patients) and heart disease treated in our CKD clinic from 2005 to 2010 and identified all patients on RAAS-I therapy who were treated with daily SPS (sorbitol-free) after episodes of hyperkalemia. Data on hospitalizations, symptoms that may be attributed to SPS therapy, and electrolyte concentration levels were obtained. Results: Fourteen patients were treated with low-dose SPS therapy for a total of 289 months (median length of follow-up, 14.5 months). None of the patients developed colonic necrosis or life-threatening events that could be attributed to SPS use. Mild hypokalemia was noted in 2 patients and responded to reducing the dose of SPS. No further episodes of hyperkalemia were recorded while patients were on the therapy. SPS was well-tolerated during the follow-up without need for withdrawal or reduction of the dose of RAAS-I therapy by any patients. Conclusions: Low-dose SPS was safe and effective as a secondary preventive measure for hyperkalemia induced by RAAS-I in CKD patients with heart disease.