Increasing attention to adolescent girls has generated an abundance of programs and a growing body of research on adolescent girls in low- and middle-income countries. Despite this, questions remain about what implementation approaches in program design are most effective, hindering efficient resource allocation, program scale-up, and replication across settings. To address these questions, we conducted a systematic review to identify lessons learned and gaps in the evidence base. We searched four electronic databases to identify studies published between 1990 and 2014 that evaluated health, social, and/or economic development programs targeting adolescent girls in low- and middle-income countries. Seventy-seven (77) studies meeting specified criteria were identified, of which 19 presented results that allowed conclusions relevant to implementation science. Studies examining the following questions were assessed: To what extent, if any, do multicomponent interventions (as opposed to single-component interventions) improve outcomes for girls? What is the added value of involving actors in addition to the girl herself such as parents, guardians, husbands (i.e., multilevel interventions)? What is the threshold proportion of girls who need to participate in a program to bring about normative and behavior changes at the community level? Is a greater level of program exposure associated with greater programmatic benefit for girls? Can supplemental “booster” activities extend the benefits of a program after it ends? We found evidence to support associations between multicomponent (vs. single component) programs, and longer program exposure (vs. less program exposure), with more favorable outcomes for girls, although both conclusions include methodological limitations. Overall, few studies assessed boosters or program saturation, and evidence on multilevel versus single-level programs was inconclusive. Few studies assessed implementation science questions by design, exposing large gaps in the evidence base. We call for future research to explicitly test such implementation science questions to inform more effective use of resources and to improve outcomes for girls.