Abstract **Background:** Geriatric polypharmacy and potentially inappropriate prescribing (PIP) represent severe iatrogenic safety challenges in sub-Saharan Africa. However, clinical quality auditing in under-resourced settings is routinely impeded by electronic health record (EHR) scarcity and data-privacy constraints. **Objective:** To generate, validate, and clinically audit a privacy-preserving synthetic cohort representing older adults in Tatale, Ghana, comparing the diagnostic yield and statistical concordance of the 2023 American Geriatrics Society (AGS) Beers and STOPP/START version 3 (v3) screening criteria. **Methods:** Utilizing the Synthea framework, a synthetic cohort of $N = 3,958$ geriatric patients ($\ge 60$ years) diagnosed with comorbid hypertension and Type 2 diabetes was generated. Demographic parameters were calibrated to the 2022 Ghana Demographic and Health Survey (GDHS; $N = 5,785$). Multidimensional validation was conducted using the first Wasserstein distance ($W_1$). Local health system vulnerabilities, including an 11.2% duplicate prescribing rate and a 27.0% stockout-driven drug substitution probability, were programmatically modeled. Automated scripts screened the cohort's medications against both criteria. Descriptive, ANOVA, and concordance (Cohen's Kappa) analyses were performed in JASP 0.97.0. **Results:** The synthetic cohort exhibited high demographic alignment with the target population ($W_1 = 15.25$ for age; simulated: 47.55% female; GDHS: 52.15% female). The baseline polypharmacy rate was 58.29% ($n = 2,307$). Programmatic screening under the STOPP criteria identified a significantly higher potentially inappropriate medication (PIM) prevalence (76.00%; 95% CI: 74.6%–77.3%) compared to the Beers criteria (49.22%; 95% CI: 47.6%–50.8%; McNemar's $p < 0.001$). Inter-criteria agreement was moderate ($\kappa = 0.469$; 95% CI: 0.446–0.492). Male sex ($\chi^2 = 58.97, p < 0.001$) and advanced age (ANOVA $F = 47.93, p < 0.001$) were associated with significantly higher medication counts. **Conclusions:** Rural older adults in secondary-care settings face severe polypharmacy and PIP exposure. Programmatic screening using STOPP/START v3 exhibits superior diagnostic sensitivity compared to the Beers criteria. Validated synthetic clinical data modeling represents a scalable, privacy-preserving, and ethically responsible methodology to audit clinical prescribing safety in data-scarce health networks.