Abstract: Computer-based and network-based methods and system that provide for evaluating medication regimen using medication-related risk assessment in an automated medication reconciliation process can comprise, without limitation, collecting comprehensive information with respect to a patient that can fill in gaps typical of claims, EHR, or HIE-based data sets, based on curated clinician review and annotation or tagging of data. Various embodiments introduce flexible use of a variety of accurate and efficient methods for capturing and characterizing medications in point-of-care settings, including structured interviews, bar code scanning, and image recognition. Embodiments of the invention can further provide for harmonizing and reconciling data from disparate sources, calculating risk based on a more comprehensive assessment and annotation of the data sets and comparing risk to create a risk offset or differential, with a subsequent tailoring of interventions based on the risk offset or differential.