Purpose Recent evidence suggests that improving the transitional care process may reduce 30-day readmissions and hospital length of stay (LOS). The objective of this study was to evaluate the impact of a pharmacist-led transitions-of-care (TOC) program on 30- and 90-day all-cause readmissions and LOS for patients discharged from the hospital acute care setting. Methods A retrospective cohort study was conducted using a difference-in-difference (DID) approach. Patients who were at least 18 years old with any of the following primary diagnoses were included: acute myocardial infarction, chronic obstructive pulmonary disease, congestive heart failure (CHF), and pneumonia. Outcome measures were all-cause 30- and 90-day readmission and LOS for the index admission. Results From October 2013 through September 2017, 1,776 patients were discharged from the intervention site, and 2,969 patients were discharged from 3 control sites. Only 33.3% of eligible patients at the intervention site actually received the intervention. The DID analysis showed that the odds ratio (OR) for 30-day readmission was 0.65 [P = 0.035] at the intervention site following TOC program initiation. The OR for 90-day readmission was 0.75 [P = 0.070]. Among all diagnosis groups, the CHF subgroup had the highest proportion of patients who actually received the TOC intervention (57.2%). Within that CHF subgroup, the ORs for 30- and 90-day readmissions were 0.52 [P = 0.056] and 0.47 [P = 0.005], respectively. The mean LOS did not change significantly in either analysis. Conclusion This pharmacist-led transitional care intervention was associated with significantly decreased inpatient readmissions. The analysis indicates that pharmacist interventions can significantly reduce 30-day readmissions for high-risk populations and 90-day readmissions in patients with CHF.