This implementation and comparative effectiveness study compared an automated call system (ACS)-assisted method to enhance staff efficiency in panel management cancer screening outreach compared with standard outreach using manual calls. One panel manager assisted by the ACS at the intervention primary care practice completed outreach workflows for 43% more patients than 2 unassisted panel managers at comparison practices, with 78% more patients in the ACS-assisted panel management program ultimately having a preventive screening gap closed. Outreach cost per completion of 1 or more cancer screenings was $45.39 under standard procedures and $15.85 using the ACS-assisted method.