Background: Allogeneic hematopoietic stem cell transplantation (HSCT) survivors experience significant psychological distress and low levels of positive psychological well-being, which can undermine patient-reported outcomes (PROs), such as quality of life (QoL). Hence, we conducted a pilot randomized clinical trial to assess the feasibility and preliminary efficacy of a telephone-delivered positive psychology intervention (Positive Affect for the Transplantation of Hematopoietic stem cells intervention [PATH]) for improving well-being in HSCT survivors. Methods: HSCT survivors who were 100 days post-HSCT for hematologic malignancy at an academic institution were randomly assigned to either PATH or usual care. PATH, delivered by a behavioral health expert, entailed 9 weekly phone sessions on gratitude, personal strengths, and meaning. We defined feasibility a priori as >60% of eligible participants enrolling in the study and >75% of PATH participants completing ≥6 of 9 sessions. At baseline and 9 and 18 weeks, patients self-reported gratitude, positive affect, life satisfaction, optimism, anxiety, depression, posttraumatic stress disorder (PTSD), QoL, physical function, and fatigue. We used repeated measures regression models and estimates of effect size (Cohen’s d ) to explore the preliminary effects of PATH on outcomes. Results: We enrolled 68.6% (72/105) of eligible patients (mean age, 57 years; 50% female). Of those randomized to PATH, 91% completed all sessions and reported positive psychology exercises as easy to complete and subjectively useful. Compared with usual care, PATH participants reported greater improvements in gratitude (β = 1.38; d = 0.32), anxiety (β = −1.43; d = −0.40), and physical function (β = 2.15; d = 0.23) at 9 weeks and gratitude (β = 0.97; d = 0.22), positive affect (β = 2.02; d = 0.27), life satisfaction (β = 1.82; d = 0.24), optimism (β = 2.70; d = 0.49), anxiety (β = −1.62; d = −0.46), depression (β = −1.04; d = −0.33), PTSD (β = −2.50; d = −0.29), QoL (β = 7.70; d = 0.41), physical function (β = 5.21; d = 0.56), and fatigue (β = −2.54; d = −0.33) at 18 weeks. Conclusions: PATH is feasible, with promising signals for improving psychological well-being, QoL, physical function, and fatigue in HSCT survivors. Future multisite trials that investigate PATH’s efficacy are needed to establish its effects on PROs in this population.