OBJECTIVES: To compare health resource utilization (HRU) among elderly patients exposed to drugs metabolized by a polymorphic drug metabolizing enzyme (DME) tested in a prospective registry for known drug-gene interaction risk (DGIR) vs. untested historical controls from Inovalon’s MORE2® database. METHODS: A retrospective cohort of historical controls age ≥65 years was identified with continuous enrollment, taking ≥3 prescription medications (July 1, 2012 - March 31, 2013) and on ≥1 drugs metabolized by a polymorphic DME. Subjects were defined as having a first claim for ≥1 drug with genetic implications or a dose change on index. Demographic, clinical and economic variables, were collected via prospective registry on tested patients and propensity score matching was conducted (matching variables: age, gender, comorbidities, and baseline medications). Patients were stratified into potential and known DGIR groups via (Genelex Youscript®) software.  Counts of HRU during 4 months follow-up post index-date included all-cause hospitalizations, emergency-room and clinic visits. RESULTS: Interim analysis of 205 tested patients with a mean age of 75 ± 7 (58% female) were compared to 82,073 historical controls (mean age 74± 6, 61% female) using t-test (p<0.0001). After matching 820 historical controls to the tested cohort, the standardized differences among the matching variables were less than 0.05. Over 90% of the total cohort has DGIR. The counts of total HRU reported among tested patients was lower compared to historical cohort (2.10 vs 2.65, respectively).  Any DGIR was associated with lower overall HRU counts among tested groups compared to controls (p=0.005). CONCLUSIONS: Based on the interim analysis, we demonstrated the value of genetic testing of drug variation in an elderly population. Higher HRU among elderly patients that were not tested may be linked to their DGIR. Routine genetic testing may result in lower HRU and their associated costs as well as improved patient care.