Background/Aims: Old age and institutionalization in care homes are associated with increased use of risk medications affecting the central nervous system (CNS). This study evaluated medication utilization and appropriateness; and assessed frailty among residents of Malaysian aged care homes. Methods: The subjects of this study included 202 elderly (≥65 years) residents of 17 aged care homes in suburban peninsular Malaysia. Frailty was measured using the Groningen Frailty Indicator (GFI) score and independence in daily living was measured as KATZ activity of daily living score. Medication appropriateness was assessed using the Medication Appropriateness Index (MAI) and 2015 Beers' criteria for Potentially Inappropriate Medication (PIM). Results: CNS medications constituted about 16% of the total, with an average of 0.8 ± 1.1 medications per resident, which reduced to 0.5 ± 0.8 medications after 3 months. Frailty (154/202) and polypharmacy (90/202) were highly prevalent in study subjects. Subjects on CNS medications had significantly higher GFI score (7.1 vs. 5.9; p = 0.031), polypharmacy (57.8 vs. 35.3%; p = 0.002), number of PIMs (0.9 vs. 0.2; p = 0.001), and mean summed MAI score (3.6 vs. 2.6; p = 0.015) than subjects not on CNS medications. Medication number was also significantly correlated with GFI (r = 0.194; p = 0.006) and KATZ (r = 0.141; p = 0.046) scores. Conclusion: Frailty and polypharmacy were highly prevalent among aged care home subjects taking CNS medications. These findings support the notion that periodic regular medication review should improve the overall use of medications in elderly patients.