Introduction: Human papillomavirus (HPV) vaccination rates nationally are low. This study determined if an electronic point-of-care prompt in the retail clinic setting increases HPV vaccination rates among an eligible population. Study design: An interrupted time series assessed change in weekly HPV vaccination rates with the introduction of an electronic point-of-care prompt and rate change in post-intervention period. Setting/participants: The study sites were two similar retail care clinics in Rochester, Minnesota. Participants were patients who presented to the retail clinics setting between the ages of 9 and 26 years from September 12, 2016, to September 30, 2017. Intervention: HPV vaccine (nonavalent) was made available at both retail clinics. Staff completed a 2-hour lecture on HPV vaccine and one-on-one training for use of the prompt. Pre- and post-intervention rates of HPV vaccination after initiation of electronic point-of-care prompt were measured. A satisfaction survey was given to all patients or parents/guardians between the ages of 9 and 26 years regardless of HPV vaccine status. Main outcome measures: HPV vaccination rates per week before and after the introduction of the electronic point-of-care prompt along with satisfaction with HPV vaccine availability and the point-of-care prompt in the retail clinic setting. Data analysis was completed January 2018. Results: The point-of-care prompt increased the median weekly HPV vaccination rate by 8.6 per 100 patient visits (95% CI=5.8, 11.5, p<0.001). Patients thought it was convenient having HPV vaccine available and helpful to be reminded of the need for HPV vaccine. Conclusions: This study demonstrates a significant increase of HPV vaccine rates in the retail clinic setting with use of a point-of-care prompt.