ABSTRACT Background Sodium and calcium polystyrene sulfonate (SPS/CPS) cation-exchange resins have had long-standing clinical use for hyperkalemia in patients with chronic kidney disease (CKD). However, uncertainty exists regarding the real-world usage of SPS/CPS for acute and chronic management of hyperkalemia. We evaluated the prescription patterns of SPS/CPS and their impact on renin–angiotensin–aldosterone system inhibitor (RAASi) treatment in patients with CKD Stages G3–G5 after an episode of de novo hyperkalemia. Methods We conducted a retrospective cohort study using population-level administrative databases in Manitoba, Canada, which included adults with CKD and a RAASi prescription who had an episode of de novo hyperkalemia (≥5.5 mmol/L) between January 2007 and December 2017. Results A total of 10 009 individuals were included in our study cohort. Among the study population, 4% received an SPS/CPS prescription within 30 days of their hyperkalemia episode. Of those, 22% received a 1-day supply of SPS/CPS and 7% received a prescription for more than 30 days. There were 8145 patients using RAASi at baseline who survived 90 days after their first hyperkalemia episode. Of those, 1447 (18%) discontinued their RAAS inhibitor and 339 (5%) received a prescription of SPS/CPS. Also, the proportion of patients who discontinued their RAASi was similar among those who did and did not receive a prescription of SPS/CPS. Conclusion In patients with CKD receiving RAASi therapy, there is a low frequency of SPS/CPS prescription after an episode of hyperkalemia. RAASi discontinuation or downtitration is the most used pharmacologic approach for the management of hyperkalemia, a strategy that deprives patients of the cardiac and renal protective benefits of RAASi. New options for the management of hyperkalemia in this population are needed.