Purpose: To assess the effectiveness of a telephone-based peer-delivered intervention in reducing distress among women with a BRCA1 or BRCA2 gene mutation. The intervention involved trained peer volunteers contacting women multiple times over a 4-month period to provide informational, emotional, and practical support. Methods: Three hundred thirty-seven participants completed the baseline questionnaire, and those reporting interest in talking to other mutation carriers were randomly assigned to either the usual care group (UCG; n = 102) or the intervention group (IG; n = 105). Participants and researchers were not blinded to group allocation. Two follow-up questionnaires were completed, one at the end of the intervention (4 months after random assignment, time 2) and one 2 months later (time 3). Outcomes included breast cancer distress (primary outcome), unmet information needs, cognitive appraisals about mutation testing, and feelings of isolation. Results: There was a greater decrease in breast cancer distress scores in the IG than UCG at time 2 (mean difference, -5.96; 95 CI, -9.80 to -2.12; P = .002) and time 3 (mean difference, -3.94; 95 CI, -7.70 to -0.17; P = .04). There was a greater reduction in unmet information needs in the IG than UCG (P <.01), with unmet needs being lower in the IG than UCG at time 2. There was a greater reduction in Cognitive Appraisals About Genetic Testing stress subscale scores in the IG than UCG (P = .02), with significantly lower scores among the IG than UCG at time 2 (P <.01). Conclusion: The intervention is effective in reducing distress and unmet information needs for this group of women. Identifying strategies for prolonging intervention effects is warranted.