Background: Preventable emergency department (ED) use may be targeted with interventions for improving the medication use process, as medication misadventures and nonadherence frequently cause preventable ED utilization. One intervention that could prevent ED visits is medication therapy management (MTM). Objective: To evaluate the effectiveness of a telephonic MTM service on reducing ED utilization within a Medicare-insured home health population. Methods: This was a secondary analysis of data from a cluster-randomized controlled trial examining hospitalizations among Medicare-insured patients within 40 randomly selected, geographically diverse, home health centers. The intervention consisted of an initial telephonic medication reconciliation with a pharmacy technician, a telephonic pharmacist-provided medication review, and follow-up pharmacist phone calls. The primary outcome of this analysis was 60-day all-cause ED utilization. Patients’ baseline risk of ED utilization was calculated, and patients were stratified into quartiles based on their baseline risk of ED utilization. Adjusted odd ratios of ED utilization were calculated. Results: Data from 656 patients (intervention n = 297, usual care n = 359) were available for this study. Overall, the MTM intervention was not associated with 60-day ED use, as 24.4% of intervention patients and 25.1% of usual care patients utilized the ED (adjusted odds ratio = 1.11; 95% confidence interval = 0.79-1.57). However, there was lower ED utilization among patients in the lowest risk-quartile (adjusted odds ratio = 2.52; 95% confidence interval = 1.15-5.49; P = .02). Conclusion: This pharmacist-delivered telephonic MTM program did not decrease ED utilization overall in a Medicare-insured home health population, but may further reduce the risk of ED utilization among patients who are at lower risk of utilization.