Background: Opioid misuse is a public health crisis. Initial opioid exposures often occur post-operatively, and 10% of opioid-naïve patients who undergo cancer surgery subsequently become long-term opioid users. It has been shown that 70% of opioids prescribed post-operatively go unused, but only 9% of unused pills are disposed appropriately, which increases the risk of unintended use. We evaluated the impact of an inexpensive, password-protected dispensing device with mail return capacity on retrieval of unused pills after cancer surgery. Methods: Adult patients scheduled for major cancer-related surgery were eligible. Enrolled patients received opioid prescriptions in a password-protected, pill-dispensing device (Addinex) from a specialty pharmacy. The mechanical device links to a smartphone app, which provides passwords on a prescriber-defined schedule. Patients request a password when they are in pain, enter the password into the device and receive a pill if the prescribed time has elapsed. The smartphone app provides clinical guidance based on patient-reported pain levels, and suggests tapering strategies. Patients are instructed to return the device in a DEA-approved mailer when opioid use is no longer required for pain control. Unused pills are destroyed upon receipt. The primary objective was to determine the feasibility of device return, defined as > 50% of patients with device return. We also explored patterns of device use, patient reported outcomes, and device satisfaction via surveys and semi-structured interviews. Results: Between October, 2020 and April, 2021, 13 patients completed the study; 4 patients are currently enrolled. Among the initial 13 patients, 7 underwent abdominal hysterectomy, 4 underwent mastectomy and 2 underwent cutaneous tumor resections. The majority of these patients (n = 10, 77%) returned the device, and more than half (n = 7, 54%) returned the device within 6 weeks of surgery. Only a minority of patients (n = 5, 38%) used the device to obtain opioids; most (n = 8, 62%) used no opioids at home, and all of these patients returned the device and the unused pills. Of 11 patients who participated in semi-structured interviews, most (n = 7, 64%) said they felt safer having opioids in the device instead of a regular pill bottle. Among device users, the majority (n = 4, 80%) reported an overall positive experience. All non-users reported having no opioid requirement for pain control. Conclusions: Our early findings suggest that use of an inexpensive, password-protected, pill-dispensing device to assist with opioid dispensing and return is feasible, with a high rate of device and unused opioid return to the pharmacy. This strategy may be effective for reducing opioid diversion. Analyses and recruitment are ongoing to evaluate the benefits of reducing post-operative opioid consumption.