Purpose Although overall success rates for treating obstructive sleep apnea (OSA) with an oral appliance (OA) are high, they are significantly higher among females. To verify published data, the study's purpose was to evaluate a participant sample after one year of OA use. The primary outcome was treatment response, with responders defined as having an apnea-hypopnea index (AHI) < 10 at follow-up and/or reduced by >= 50% of baseline. Secondary measures were from standardized questionnaires. Methods A sample of 314 participants, predominately with moderate-to-severe OSA, were enrolled and instructed to use an OA every night. At baseline and one-year follow-up, polygraphic recordings and questionnaires, including sleepiness (measured using the Epworth sleepiness scale) and quality-of-life (measured using the Functional Outcomes of Sleep Questionnaire), were collected. Results Among the 314 participants, 192 completed the one-year evaluation: 51 females (27%) and 141 males (73%). Overall, OA treatment resulted in 78% and 77% responders among females and males, respectively. Neither the difference in improvement nor the absolute change in AHI differed significantly based on gender, at any OSA severity level. There were no significant gender differences in sleepiness or quality of life. Treatment-related adverse reactions were more common among females. Conclusion Both females and males with OSA respond well to OA therapy, with nonsignificant gender differences in outcomes. Thus, the hypothesis that females respond better to OA treatment is rejected.