Background: Vaccine misinformation has been widely spread on social media, but attempts to combat it have not taken advantage of the attributes of social media platforms for health education. Methods: The objective was to test the efficacy of moderated social media discussions about COVID-19 vaccines in private Facebook groups. Unvaccinated U.S. adults were recruited using Amazon's Mechanical Turk and randomized. In the intervention group, moderators posted two informational posts per day for 4 weeks and engaged in relationship-building interactions with group members. In the control group, participants received a referral to Facebook's COVID-19 Information Center. Follow-up surveys with participants (N = 478) were conducted 6 weeks post-enrollment. Results: At 6 weeks follow-up, no differences were found in vaccination rates. Intervention participants were more likely to show improvements in their COVID-19 vaccination intentions (vs. stay same or decline) compared with control (p = .03). They also improved more in their intentions to encourage others to vaccinate for COVID-19. There were no differences in COVID-19 vaccine confidence or intentions between groups. General vaccine and responsibility to vaccinate were higher in the intervention compared with control. Most participants in the intervention group reported high levels of satisfaction. Participants engaged with content (e.g., commented, reacted) 11.8 times on average over the course of 4 weeks. Conclusions: Engaging with vaccine-hesitant individuals in private Facebook groups improved some COVID-19 vaccine-related beliefs and represents a promising strategy.