There is a need to increase the armamentarium of pharmacotherapies for alcohol use disorder (AUD). Recent research suggests that mineralocorticoid receptor (MR) antagonism via spironolactone may represent a novel pharmacological treatment for AUD. We conducted a pharmacoepidemiologic retrospective cohort study (June 1, 2014 to May 31, 2018) to examine whether spironolactone dispensation (≥90 continuous days), for any indication, is associated with changes in weekly alcohol use about 6 months later. We compared 523 spironolactone-treated adults and 2305 untreated adults, matched on high-dimensional propensity scores created from a set of predefined (sociodemographic and health characteristics, diagnoses, and service utilization) and empirical electronic health record-derived covariates. The sample was 57% female and 27% non-White with a mean age of 59.2 years (SD = 19.3). Treated patients reduced their weekly alcohol use by 3.50 drinks (95% CI = -4.22, -2.79), while untreated patients reduced by 2.74 drinks (95% CI = -3.22, -2.26), yielding a significant difference of 0.76 fewer drinks (95% CI = -1.43, -0.11). Among those who drank >7 drinks/week at baseline, treated patients, compared to untreated patients, reported a greater reduction in weekly alcohol use by 4.18 drinks (95% CI = -5.38, -2.97), while there was no significant difference among those who drank less. There was a significant dose-response relationship between spironolactone dosage and change in drinks/week. Pending additional evidence on its safety and efficacy in individuals with AUD, spironolactone (and MR blockade, at large) may hold promise as a pharmacotherapy for AUD.