Women and men diagnosed with infertility experience a variety of infertility-related stressors, including changes to their family and social networks, strain on their sexual relationship, and difficulties and unexpected challenges in their relationship. Infertility stress is linked with depression and psychological distress, and can lead to premature dropout from medical treatments and unresolved feelings of loss and grief. The current study examined the effectiveness of treating infertility stress using Acceptance and Commitment Therapy (ACT), a promising new behavior therapy that targets experiential avoidance through mindfulness, acceptance strategies, and value-directed action. This single-case study followed a couple experiencing infertility-related stress following a failed in vitro fertilization (IVF) procedure. The couple completed 6 self-report measures at 7 time points, including a second failed IVF attempt and a 1-year follow-up. Measures included both distress-focused instruments and therapy process-related questionnaires. The female participant reported higher pretreatment stress and depression scores compared to her partner. She reported significant decreases in global infertility stress, social infertility stress, sexual infertility stress, psychological distress, and depression from pretherapy to 1-year follow-up. She also reported a decrease in infertility stress following her second failed in vitro fertilization (IVF) attempt. The male participant reported significant decreases in sexual infertility stress. The study suggests that acceptance-based therapy shows promise in treating infertility stress in patients experiencing infertility who undergo medical treatments. The data from this preliminary case study also suggest that ACT may be helpful for couples following IVF treatment failure. Treatment gains were maintained 1-year posttherapy, indicating that an ACT approach to treating infertility has the potential to produce lasting change. (Contains 4 figures and 1 table.)