Objectives: This study investigated the impact of the Medtronic AdaptivCRT (aCRT) (Medtronic, Mounds View, Minnesota) algorithm on 30-day readmissions after heart failure (HF) and all-cause index hospitalizations. Background: The U.S. Hospital Readmission Reduction Program, which includes a focus on HF, reduces Medicare inpatient payments when readmissions within 30 days of discharge exceed a moving threshold based on national averages and hospital-specific risk adjustments. Internationally, readmissions within 30 days of any discharge may attract reduced or no payment. Recently, cardiac resynchronization therapy (CRT) devices equipped with the aCRT algorithm allowing automated ambulatory device programming were introduced. The Adaptive CRT trial demonstrated the algorithm s safety and comparable outcome against a rigorous echocardiography-based optimization protocol. Methods: We analyzed data from the Adaptive CRT trial, which randomized patients undergoing CRT defibrillation on a 2:1 basis to aCRT (n = 318) or to CRT with echocardiographic optimization (Echo, n = 160) and followed up these patients for a mean of 20.2 months (range: 0.2 to 31.3 months). Logistic regression with generalized estimating equation methodology was used to compare the proportion of patients hospitalized for HF and for all causes who had a readmission within 30 days. Results: For HF hospitalizations, the 30-day readmission rate was 19.1 (17 of 89) in the aCRT group and 35.7 (15 of 42) in the Echo group (odds ratio: 0.41; 95 confidence interval [CI]: 0.19 to 0.86; p = 0.02). For all-cause hospitalization, the 30-day readmission rate was 14.8 (35 of 237) in the aCRT group compared with 24.8 (39 of 157) in the Echo group (odds ratio: 0.54; 95 CI: 0.31 to 0.94; p = 0.03). The risk of readmission after HF or all-cause index hospitalization with aCRT was also significantly reduced beyond 30 days. Conclusions: Use of the aCRT algorithm is associated with a significant reduction in the probability of a 30-day readmission after both HF and all-cause hospitalizations. (Adaptive Cardiac Resynchronization Therapy Study [aCRT]; NCT00980057).