Objective: To compare the quality of life (QoL), a measure of psychological well-being, of adolescents reared in lesbian-mother families with that of a matched comparison group of adolescents with heterosexual parents. The adolescents in the comparison group were derived from a representative sample of adolescents in Washington state. The second aim of the study was to assess among teens with lesbian mothers whether donor status, maternal relationship continuity, and self-reported stigmatization are associated with QoL. Methods: In 1986, prospective lesbian mothers were recruited in Boston, Washington, DC, and San Francisco. Currently, 93% of the National Longitudinal Lesbian Family Study (NLLFS) families are still participating in the study. This report is based on an online questionnaire completed by 78 NLLFS adolescent offspring—39 girls and 39 boys. Six items of the Youth Quality of Life Instrument were used to assess QoL. Also, the NLLFS adolescents were asked whether they had experienced stigmatization, and if so, to describe these experiences (e.g., teasing and ridicule). Mothers were queried about donor status and maternal relationship continuity. Results: The results revealed that the NLLFS adolescents rated their QoL comparably to their counterparts in heterosexual-parent families. Donor status, maternal relationship continuity, and experienced stigmatization were not related to QoL. Conclusion: Adolescent offspring in planned lesbian families do not show differences in QoL when compared with a matched group of adolescents reared in heterosexual families. By investigating QoL, this study provides insight into positive aspects of mental health of adolescents with lesbian mothers.