Measurement of Quality of Life (QOL) forms an integral part in assessing disease and treatment impact from the patient’s perspective. While prior studies compare the QOL of patients with primary aldosteronism (PA) undergoing surgical management compared with pharmacotherapy, there is little published data comparing different pharmacological regimens and effect on QOL. Their varying mechanism of action, side effect profile and efficacy may contribute to different QOL outcomes. An online survey was distributed through international PA patient support groups to assess patient demographics, baseline health status and QOL. Using the validated 36-Item Short-Form Health Survey (SF-36), as well as a PA-specific questionnaire, we compared the QOL outcomes of patients with PA treated with mineralocorticoid receptor antagonists (MRA, spironolactone or eplerenone) and patients treated with epithelial sodium channel inhibitors (ENaCi, amiloride). Seventy-nine patients with medically-managed PA (73 taking MRA, 82% female; 6 taking ENaCi, 100% female; mean age 36 years) completed the survey. There were no significant differences in the body mass index, blood pressure, total number of medications and total number of comorbidities between the treatment groups. SF-36 scale scores of patients taking MRA tended to be greater in the domains of role-emotional and mental health compared to those taking ENaCi (62.1 vs 44.4, 61.6 vs 53.3) but lower in the domain of general health (37.5 vs 52.5). However, the differences did not reach statistical significance. The PA-specific QOL questionnaire tended to demonstrate higher QOL in the domain of “fluid balance” in patients taking MRA, without being statistically significant (6 vs 8). No significant difference was observed in SF-36 domains or PA-specific questionnaire between patients taking spironolactone or eplerenone. This study demonstrated trends towards differences in specific QOL domains between patients treated with MRA or ENaCi. A larger sample size is required to ascertain the statistical significance of these differences.