Studies suggest that continuous long-term use of patiromer by patients with hyperkalemia is associated with less health care resource utilization compared with not using potassium binders. To retrospectively evaluate health care resource utilization and costs with longer-term adherent vs short-term use of patiromer. Time-restricted extracts from Optum's de-identified Clinformatics® Data Mart Database (CDM; January 2016-May 2019) and Symphony Health (SHA; January 2016-September 2018) deidentified databases were analyzed. Both include participants enrolled in commercial and privatized public insurance programs (SHA includes some government programs). Both integrate health care claims data from medical and pharmacy claims. Patients aged 18 years or older with hyperkalemia and an index patiromer prescription were selected. Patiromer use was identified as short-term (<2 months) and any fill quantity or adherent longer-term with claims for at least 2 consecutive months and fill quantities of at least 80% of the total days. Groups were matched on multiple categorical covariates to control for demographic variables, baseline characteristics, and markers of disease severity. Random sampling without replacement was performed 50 times to identify 50 sets of patients matched from the short-term cohort to the longer-term cohort. Health care costs/charges and encounters were compared for a 6-month post-index period using t-tests. Of the CDM patients, 1,267 (40.2%) vs 1,887 (59.8%) and of the SHA patients, 2,234 (35.1%) vs 4,132 (64.9%) experienced longer-term vs short-term patiromer use, respectively. Patient sampling selected 242 and 485 patient-matched pairs from CDM and SHA databases, respectively. At 6 months post-index in longer-term vs short-term patiromer groups (P < 0.0001 for all differences shown), respective mean medical and prescription costs/charges were $42,000 vs $54,311 (-$12,311) and $6,816 vs $4,786 (+$2,030), respectively, for CDM patients and $75,147 vs $84,414 (-$9,267) and $4,689 vs $3,736 (+$953) for SHA patients. In the CDM database, medical costs were lower for longer-term vs short-term cohorts for end-stage renal disease services charges ($10,342 vs $14,976 [-$4,634]), inpatient charges ($15,789 vs $21,473 [-$5,684]), and office visit charges ($10,152 vs $13,152 [-$3,000]). Patient out-of-pocket costs ($658 vs $420 [+$238]) and total prescription charges ($6,158 vs $4,366 [+$1,792]) were higher for the longer-term cohort of CDM patients, with similar findings in the SHA dataset. Adherent, longer-term use of patiromer is associated with significantly lower medical costs offsetting higher prescription costs, driven by the largest changes in inpatient and clinic services at CDM and SHA, respectively. This illustrates an economic value of longer-term adherence to patiromer.