Seamless care is the desirable continuity of care delivered to a patient in the healthcare system across the spectrum of caregivers and their environments. Medication Reconciliation is one component of seamless pharmaceutical care. A randomized controlled trial, carried out over nine months with a six-month follow-up period, investigated the impact of a pharmacist-directed seamless care service. Intervention patients admitted to one of two general medicine units were subjected to a comprehensive seamless care discharge process as they were discharged from a regional, academically affiliated hospital in Moncton, NB. The number, type and potential clinical impact of drug-therapy problems for seamless monitoring (DTPsm) and drug-therapy inconsistencies and omissions (DTIOs) in hospital discharge medications were measured. A total of 253 patients, with 134 patients in the intervention group and 119 in the control group, completed the study. An average of 3.59 DTPsm per intervention patient, with 72.1% of these being scored as having a significant or very significant clinical impact level, were communicated to community pharmacists. Ninety-nine DTIOs were identified and resolved in intervention patients before discharge. A retrospective medical chart review demonstrated that the intervention resolved almost all DTIOs. In conclusion, a pharmacist-directed seamless care service had a significant impact on drug-related clinical outcomes and processes of care.