Sickle cell disease (SCD) genetic knowledge is important when individuals make reproductive decisions. This study assessed feasibility and efficacy of delivering basic genetic information to 101 adolescents with SCD. Participants completed a questionnaire to test SCD genetic knowledge at 3 timepoints: before genetic education session (pretest), after the session (posttest), and 6 months later (follow-up). Scores at 3 timepoints were compared by Wilcoxon signed-rank tests, and group differences were compared by Wilcoxon-Mann-Whitney and Kruskal-Wallis tests. Participants’ median scores significantly increased from pretest to posttest and from pretest to follow-up. Males had a greater change in scores than females. Scores decreased slightly from posttest to follow-up. Participants with HbSS/HbSβ0-thal genotype and participants with more prior pain episodes exhibited a smaller increase in median scores than those with HbSC/HbSβ+-thal genotype and no prior pain history; however, all groups had substantial gains from pretest to posttest and follow-up tests demonstrating that adolescents with SCD can learn basic genetics. This study established that genetic education can successfully be incorporated in transition to adult care programs for adolescents with SCD. Genetic education should be included in the standard plan of care for adolescents with SCD to assist them in making informed reproductive choices.