OBJECTIVES: Evidence-based, consensus-driven clinical pathways are increasingly recognized as a critical component of new delivery models and reimbursement methodologies including medical homes, accountable care organizations, episode-of-care payment, and bundled payment. Providers may also have to negotiate multiple payer-specific pathways that are increasingly complex as a result of targeted precision medicine. Decision support tools (DST) have been considered one solution to navigate this complexity and optimize pathway compliance. We report on pathway compliance variance related with or without use of a point-of-care, real-time oncology specific DST. METHODS: From 1/1/2012 to 12/31/2013, 38 oncologists from 15 practices participating in a payer-sponsored oncologist-developed cancer pathway program incorporated use of a proprietary real-time, point-of-care DST. Program participation and use of the DST was voluntary, but enhanced remuneration was provided to mitigate additional work. Retrospective data collection from fully adjudicated claims and from the DST was collected and compared quarterly from 10/1/12 to 6/30/14. Physician chemotherapy regimen selections over the study period were reviewed for compliance to the consensus pathways. A 2-proportion z-test was used for data analysis. RESULTS: Of the 798 physician-generated chemotherapy selections ordered during the study period, 31% were registered in the point-of-care DST. The majority (69%) were only found upon claims review. Pathway compliance for chemotherapy was 99% for the 250 regimens selected through the DST and 89% for the 548 regimens identified through claims analysis only (p <.05). CONCLUSIONS: Use of a real-time, point-of-care DST can significantly enhance pathway compliance, but low adoption rates and usage limit the current benefit of this technology. Further research is needed to identify barriers to real-time, point-of-care DST adoption, which include impact on workflow, redundancy to electronic medical record, and perceptions of intrusion.