Adverse drug reactions (ADRs) contribute to hospitalization but data on its economic burden is scant. Pre-emptive pharmacogenetic (PGx) testing can potentially reduce ADRs and its associated costs. The objectives of this study were to quantify the economic burden of ADRs and to estimate the breakeven cost of pre-emptive PGx testing in Singapore. We collected itemized costs for 1000 random non-elective hospitalizations of adults admitted to a tertiary-care general hospital in Singapore. The presence of ADRs at admission and their clinical characteristics were reported previously. The economic burden of ADRs was assessed from two perspectives: (1) Total cost and (2) incremental costs. The breakeven cost of PGx testing was estimated by dividing avoidable hospitalization costs for ADRs due to selected drugs by the number of patients taking those drugs. The total cost of 81 admissions caused by ADRs was US570,404.Costsweresignificantlyhigherforbleeding/elevatedinternationalnormalizedratio(US9906 vs. US2251,p= 6.58 × 10−3)comparedtootherADRs,andfordrugsactingonthebloodcoagulationsystem(US9884 vs. US2229,p= 4.41 × 10−3)comparedtootherdrugclasses.TherewerehigherincrementallaboratorycostsduetoADRscausingorbeingpresentatadmission.Theestimatedbreakevencostofapre−emptivePGxtestforpatientstakingwarfarin,clopidogrel,chemotherapeuticandneuropsychiatricdrugswasUS114 per patient. These results suggest that future studies designed to directly measure the clinical and cost impact of a pre-emptive genotyping program will help inform clinical practice and health policy decisions