Direct renin concentration is replacing plasma renin activity in many laboratories for the investigation of primary aldosteronism, which may have a significant impact on the resulting aldosterone:renin ratios. We sought to develop a population-based approach to establishing an aldosterone:renin ratio cutoff when transitioning between assays. A population-based study was performed in Calgary, Alberta, Canada of 4301 individuals who received testing from January 2012 to November 2015. In 2014, direct renin concentration replaced plasma renin activity in routine testing. We described the prevalence of primary aldosteronism in our population before the change and, using the assumption of disease prevalence stability, determined the corresponding ratio cutoffs after the introduction of the new assay. During the initial portion of the study (using plasma renin activity), 4.9% of those screened were classified as highly probable cases, whereas 10.4% were considered probable and 28.9% possible using locally validated cutoffs. Aldosterone:renin ratio cutoffs were then determined for the direct renin concentration assay. A highly probable case of primary aldosteronism corresponded to a cutoff of >100 pmol L ⁻¹ mIU ⁻¹ L ⁻¹ with hypokalemia. A probable case corresponded to a cutoff of >100 and a possible case to >35 pmol L ⁻¹ mIU ⁻¹ L ⁻¹ . In contrast, cutoffs derived using a conversion factor resulted in significantly higher cutoffs and the potential for missed cases. In conclusion, using large population data, historically consistent aldosterone:renin ratio cutoffs can be established when transitioning between assays. Population-derived cutoffs may be more appropriate for clinical use and less likely to result in false-negative classification than those obtained from conventional direct method comparisons.