This study examines the geospatial and intertemporal impact of Ghana’s National Health Insurance Scheme (NHIS) on household health expenditure using nationally representative data from the 2022 Annual Household Income and Expenditure Survey (AHIES). Employing propensity score matching (PSM) to control for selection bias, the analysis reveals that NHIS significantly reduces health spending across most of Ghana’s 16 regions, with Greater Accra, Ashanti, and Central showing the largest impacts. However, regional disparities persist, with Volta Region showing no statistically significant effect. Temporally, the scheme’s effectiveness also varies, with the largest cost reductions observed in the fourth quarter of 2022, suggesting seasonal sensitivity in healthcare access and NHIS performance. The findings underscore the need for region-specific interventions, improved service delivery, and stronger inter-ministerial coordination, particularly among the Ministry of Health, NHIA, and Ghana Health Service to ensure equitable and consistent financial protection for all households, especially the poor and vulnerable ones.