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Background: Women’s College Hospital (WCH) offers specialized surgical procedures, including ambulatory breast reconstruction in post-mastectomy breast cancer patients. Most patients receiving ambulatory surgery have low rates of postoperative events necessitating clinic visits. Increasingly, mobile monitoring and follow-up care is used to overcome the distance patients must travel to receive specialized care at a reduced cost to society. WCH has completed a feasibility study using a mobile app (QoC Health Inc, Toronto) that suggests high patient satisfaction and adequate detection of postoperative complications. Objective: The proposed cost-effectiveness study models the replacement of conventional, in-person postoperative follow-up care with mobile app follow-up care following ambulatory breast reconstruction in post-mastectomy breast cancer patients. Methods: This is a societal perspective cost-effectiveness analysis, wherein all costs are assessed irrespective of the payer. The patient/caregiver, health care system, and externally borne costs are calculated within the first postoperative month based on cost information provided by WCH and QoC Health Inc. The effectiveness of telemedicine and conventional follow-up care is measured as successful surgical outcomes at 30-days postoperative, and is modeled based on previous clinical trials containing similar patient populations and surgical risks. Results: This costing assumes that 1000 patients are enrolled in bring-your-own-device (BYOD) mobile app follow-up per year and that 1.64 in-person follow-ups are attended in the conventional arm within the first month postoperatively. The total cost difference between mobile app and in-person follow-up care is $245 CAD ($223 USD based on the current exchange rate), with in-person follow-up being more expensive ($381 CAD) than mobile app follow-up care ($136 CAD). This takes into account the total of health care system, patient, and external borne costs. If we examine health care system costs alone, in-person follow-up is $38 CAD ($35 USD) more expensive than mobile app follow-up care over the first postoperative month. The baseline difference in effect is modeled to be zero based on clinical trials examining the effectiveness of telephone follow-up care in similar patient populations. An incremental cost-effectiveness ratio (ICER) is not reportable in this scenario. An incremental net benefit (INB) is reportable, and reflects merely the cost difference between the two interventions for any willingness-to-pay value (INB=$245 CAD). The cost-effectiveness of mobile app follow-up even holds in scenarios where all mobile patients attend one in-person follow-up. Conclusions: Mobile app follow-up care is suitably targeted to low-risk postoperative ambulatory patients. It can be cost-effective from a societal and health care system perspective. [J Med Internet Res 2014;16(9):e213]