OBJECTIVES:  Polypharmacy is a widely known risk factor for adverse drug reactions, drug-drug interactions, and low adherence in the elderly population. There remains a paucity of evidence demonstrating its effect on hospital admissions and costs. This study aims to determine the effects of polypharmacy on hospital admissions and hospital costs among older patients in Thailand. METHODS: A retrospective cohort study was conducted using an electronic patient database in a provincial hospital of Thailand . All patients aged 60 years or older with at least 2 visits during 2009 were included. Exposure of interest is polypharmacy and excessive polypharmacy which were defined as dispensed medications for more than five and ten items, respectively. Outcomes of interest are hospital admissions and hospitalization costs incurred after index date of polypharmacy.  We performed two-part model and used poisson regression and log-transformed linear regression with Duan’s smearing estimator to determine the effects of polypharmacy on hospital admissions rate and hospitalization costs, respectively. All analyses were adjusted for potential confounders and propensity score. RESULTS: A total of 17,787 elderly patients were included. The mean age was 71 years with 57% female. Forty-two and 12 percent of patients received polypharmacy and excessive polypharmacy, respectively. Excessive polypharmacy was significantly associated with increased risk of admission (adjusted incidence rate ratio (IRR): 3.2 (95% CI; 1.1-5.4)) while only increased trend of admission was found among polypharmacy (IRR: 1.5 (95% CI; 0.9-2.1), Hospitalization costs were significantly higher at $135 (95% CI; 111.0 – 159.0) and $25.0 (95% CI; 16.1 – 38.0) for excessive polypharmacy and polypharmacy, compared with non-polypharmacy. CONCLUSIONS: Both polypharmacy and excessive polypharmacy have significantly elevated healthcare costs but only excessive polypharmacy is significantly associated with increased risk of hospital admission. These findings demonstrated the detrimental effects of polypharmacy and highlighted the importance of finding measures to reduce polypharmacy