Background: Since December 2010, online computerized prospective drug utilization review (pDUR) has been implemented in Korea. pDUR involves the review of each prescription before the medication is dispensed to the individual patient. The pDUR is performed electronically by Health Insurance Review & Assessment Service (HIRA), which is a Korean governmental agency, and then HIRA provides medical institutions and pharmacies with information that can be helpful to them in preventing potential drug problems such as drug/drug interactions or ingredient duplication. The aim of this study was to assess the impact of the Korean pDUR implementation on the proportion of drug-drug interactions (DDIs) using claims data from HIRA. Methods: A before-after comparison of the prevalence of DDIs between prescription was conducted, using HIRA administrative claims data of medical institution from January 2010 to December 2011. The analysis unit was the prescription issued and pairs before and after. The main outcome measures were the proportion of DDIs within- (control group) or between- physician encounters. To examine the difference, a paired t-test was applied. Results: We found that DDIs proportion between prescription decreased significantly (t=3.04, p=0.0026) after the implementation of pDUR, whereas there is no significant reduction within prescription (t=1.15, p=0.2518). With respect to the prevalence of DDIs between drug groups, the most dramatic reduction was occurred between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and anti-fungal agents. Conclusion: It seems effective that giving a direct feedback to prescribers by a prospective DUR. Further research is needed to assess the impact of DUR to final outcomes such as hospitalization.