Virtual world environments have the potential to increase access to diabetes self-management interventions and may lower cost. We tested the feasibility and comparative effectiveness of a virtual world versus a face-to-face diabetes self-management group intervention. We recruited African American women with type 2 diabetes to participate in an 8-week diabetes self-management program adapted from Power to Prevent, a behavior-change in-person group program for African Americans with diabetes or pre-diabetes. The program is social cognitive theory-guided, evidence-based, and culturally tailored. Participants were randomized to participate in the program via virtual world (Second Life) or face-to-face, both delivered by a single intervention team. Blinded assessors conducted in-person clinical (HbA1c), behavioral, and psychosocial measurements at baseline and 4-month follow-up. Pre-post differences within and between intervention groups were assessed using t tests and chi-square tests (two-sided and intention-to-treat analyses for all comparisons). Participants (N=89) were an average of 52 years old (SD 10), 60% had ≤high school, 82% had household incomes <US $30,000, and computer experience was variable. Overall session attendance was similar across the groups (6.8/8 sessions, P=.90). Compared to face-to-face, virtual world was slightly superior for total activity, light activity, and inactivity (P=.05, P=.07, and P=.025, respectively). HbA1c reduction was significant within face-to-face (-0.46, P=02) but not within virtual world (-0.31, P=.19), although there were no significant between group differences in HbA1c (P=.52). In both groups, 14% fewer patients had post-intervention HbA1c ≥9% (virtual world P=.014; face-to-face P=.002), with no significant between group difference (P=.493). Compared to virtual world, face-to-face was marginally superior for reducing depression symptoms (P=.051). The virtual world intervention costs were US $1117 versus US $931 for face-to-face. It is feasible to deliver diabetes self-management interventions to inner city African American women via virtual worlds, and outcomes may be comparable to those of face-to-face interventions. Further effectiveness research is warranted. ClinicalTrials.gov NCT01340079; http://clinicaltrials.gov/show/NCT01340079 (Archived by WebCite at http://www.webcitation.org/6T2aSvmka).