In a quasi-experimental study, decision support software was installed in three hospitals to study the ability to scale (spread) its use from one hospital on paper to three hospitals as software, and to examine the effect on 30- and 60-day readmissions. The Discharge Decision Support System (D2S2) software analyzes data collected by nurses on admission with a proprietary risk assessment tool, identifies patients in need of post-acute care, and alerts discharge planners. On six intervention units, with a concurrent comparison group of 76 units, we examined the implementation experience and compared readmission outcomes before and after implementation. The software implementation finished one month ahead of schedule, and the software performed reliably. High-risk patients admitted in the experimental phase after implementation of D2S2 decision support had significantly fewer 30-day readmissions (a decrease from 22.2% to 9.4%). When high- and low-risk patients were analyzed together, D2S2 achieved a 33% relative reduction in 30-day readmissions (13.1 to 8.8%) and sustained a 37% relative reduction at 60 days. The software, available commercially through RightCare Solutions, was adopted by the health system and remains in use after 22 months. The D2S2 risk assessment tool can be installed easily in existing EHR systems. Future research will focus on how the tool influences discharge decision-making and how its accuracy can be improved in specific settings. © 2015 Wiley Periodicals, Inc.