Objective To evaluate the effectiveness of a telephonic medication therapy management (MTM) service on reducing hospitalizations among home health patients. Setting Forty randomly selected, geographically diverse home health care centers in the United States. Design Two‐stage, randomized, controlled trial with 60‐day follow‐up. All Medicare‐ insured home health care patients were eligible to participate. Twenty‐eight consecutive patients within each care center were recruited and randomized to usual care or MTM intervention. The MTM intervention consisted of the following: (1) initial phone call by a pharmacy technician to verify active medications; (2) pharmacist‐provided medication regimen review by telephone; and (3) follow‐up pharmacist phone calls at day seven and as needed for 30 days. The primary outcome was 60‐day all‐cause hospitalization. Data Collection Data were collected from in‐home nursing assessments using the OASIS‐C. Multivariate logistic regression modeled the effect of the MTM intervention on the probability of hospitalization while adjusting for patients’ baseline risk of hospitalization, number of medications taken daily, and other OASIS‐C data elements. Principal Findings A total of 895 patients (intervention n = 415, control n = 480) were block‐randomized to the intervention or usual care. There was no significant difference in the 60‐day probability of hospitalization between the MTM intervention and control groups (Adjusted OR: 1.26, 95 percent CI: 0.89–1.77, p = .19). For patients within the lowest baseline risk quartile (n = 232), the intervention group was three times more likely to remain out of the hospital at 60 days (Adjusted OR: 3.79, 95 percent CI: 1.35–10.57, p = .01) compared to the usual care group. Conclusions This MTM intervention may not be effective for all home health patients; however, for those patients with the lowest‐risk profile, the MTM intervention prevented patients from being hospitalized at 60 days.