Background: There have been multiple reported pharmacy initiatives to reduce opioid misuse and accidental overdose to address our nation’s public health crisis. To date, there has not been a description in the literature of a community pharmacy follow-up initiative for dispensed opioids. Methods: A follow-up program was designed and implemented in community pharmacies as part of a previously developed opioid overdose and misuse prevention program (ONE Program). Five to twelve days after the dispensing of an opioid, pharmacy technicians called the patient to follow up on opioid safety topics. Pharmacy technicians used a questionnaire to inquire about medication disposal plans, if the patient was taking the medication more than prescribed, medication side effects, and if the patient needed a pharmacist consultation. The results from that questionnaire were documented. Results: During the first 18 months of the follow-up program, 1789 phone calls were completed. Of those contacted, 40% were still using their opioid medication, and over 10% were experiencing side effects which triggered a pharmacist consult. Patients were reminded of proper medication disposal methods, and most patients (78%) desired to dispose of unused medication at the pharmacy medication disposal box. Conclusions: Follow-up phone calls post-opioid medication dispensing were shown to add value to a previously established opioid misuse and accidental overdose prevention program and allowed for the fulfillment of the Pharmacist Patient Care Process.