This study aims to investigate whether Girl2Girl, a text messaging-based pregnancy prevention program for cisgender LGB+ girls, had different effects on subgroups based on age, sexual identity, and experience with penile-vaginal sex. A total of 948 girls, 14–18 years old, were recruited nationally via social media and enrolled over the telephone. Once they completed the baseline, they were randomized to either Girl2Girl or an attention-matched control program that discussed “healthy lifestyle” topics (e.g., self-esteem). Both programs were 5 months long: Girls received daily messages for 8 weeks, and then went through a “latent” period of 3 months, and finished with a 1-week review. Outcome measures included condom-protected sex, uptake of other types of birth control, abstinence, and pregnancy. Measures were collected at baseline; 3-month, 6-month, 9-month, and 12-month post-intervention end, which was 17 months after enrollment. Effect modification was examined using longitudinal mixed effects models. Overall, results suggested significant moderating effects of age,(f2 = .12), sexual identity (f2 f2 = .11) on rates of condom use and use of other contraception. Although there were no significant moderating effects on pregnancy, abstinence, or intentions to use condoms, use birth control, or be abstinent, (p’s > .16), patterns of effects were in the same direction as for significant findings. For example, at 9-month post-intervention, among those who identified as bisexual, the incidence rate of protected sex events was 39% higher for intervention vs. control (IRR = 1.39, 95% CI: 1.06–2.70), adjusting for baseline rate of condom use and sexual experience. Similarly, at 12 months, among bisexual participants, intervention participants had a significantly higher IRR of condom-protected sexual events (IRR = 2.65, 95% CI: 1.31–5.34). There were also higher odds of uptake of birth control use other than condoms for intervention vs. control at 6- (OR = 1.10, 95% CI: 1.01–1.77), 9 m (OR = 1.11, 95% CI: 1.07–1.89), and 12-month (OR = 1.13, 95% CI: 1.07–1.78) follow-up. Girl2Girl appears to be particularly effective for older adolescents, bisexual girls, and those who have already had penile-vaginal sex. No one single approach is going to affect teen pregnancy. Instead, it is more likely that different intervention content and delivery methods will be more accessible and salient to some but not other youth. Understanding for whom the intervention works is just as important as understanding for whom the intervention does not, as this can inform opportunities for future intervention development.Clinical Trial Registration: ClinicalTrials.gov ID# NCT03029962.