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Patients frequently experience suboptimal transitions from the hospital to the community, which can increase the likelihood of readmission. It is not known which care coordination services can lead to improvements in readmission rates. To evaluate the effects of two care coordination interventions on 30-day readmission rates. Prospective multicenter observational study of hospitalized patients eligible for two care coordination services between January 1, 2013, and October 31, 2015. Readmission rates were compared for patients who received each care coordination intervention versus those who did not using multivariable generalized estimating equation logistic regression models. A total of 25,628 patients hospitalized in medicine, neurosciences, or surgical sciences units. Patients discharged home and deemed to be at high risk for readmission were assigned a nurse Transition Guide (TG) for 30 days post-discharge. All other patients were assigned the Patient Access Line (PAL) intervention, which provided a post-discharge phone call from a registered nurse. Two large academic hospitals in Baltimore, MD. Thirty-day all-cause readmission to any Maryland hospital. Among all patients, 14.2% (2409/16,993) of those referred for the PAL intervention and 22.8% (1973/8635) of those referred for the TG intervention were readmitted. PAL-referred patients who did not receive the intervention had an adjusted odds ratio (aOR) for readmission of 1.27 (95% confidence interval [95% CI] 1.12–1.44, p