Background: Given the 3.1 million breast cancer survivors in America, quality of life (QoL) is a vital issue. Bio-psychosocial milieu of survivorship is increasingly important. This study assesses the impact of bio-psychosocial intervention (BPSI) on the QoL of breast cancer survivors utilizing Functional Assessment of Cancer Therapy -Breast (FACT-B) instrument. Methods: A prospective randomized trial was designed; intervention arm included a 4-hour BPSI coping skills class; control arm received standard of cancer (SOC) and follow up care. Women diagnosed within 2 years of study initiation were eligible. Sample size was based on 8-point difference in FACT-B score, 90% power, 5% type I error, and 20% attrition. FACT-B questionnaire was administered to all patients at baseline and at 6-month intervals. SAS 9.3 software was used to analyze data using Chi-square test for categorical and Wilcoxon rank sum for ordinal data; linear mixed modeling was used for longitudinal analysis. Results: One hundred and three of 120 (86%) patients were available for analysis. Forty-seven patients were in BSPI arm, and 56 received SOC. For BPSI arm vs. SOC arm, the median (interquartile) age [60 (52, 68) vs. 58 (52, 68)yrs. P = .9135], cancer-stage (0: 1: 2: 3 = 11%: 41%: 35%: 13% vs. 18%: 46%: 22%: 15%, P = .4645), and biology (triple-negative: HER2+ : ER+ = 9%: 74%: 17% vs. 8%: 72%: 20%, P = .8454), respectively, was similar. Mean (SE) FACT-B scores in BPSI vs. SOC arms at 6 months and 1 year were 115.1 (2.2) vs. 114.6 (2.0) (P = .8731) and 124.7(2.8) vs. 101.4 (2.4) (P = .0001). The inter-group difference significantly expanded at 1 year (P = .0001). The 12-month difference persisted when confounding baseline variables were adjusted for in in multivariate modeling. Conclusion: BPSI coping skills class significantly improved the QoL of breast cancer survivors by one year post-intervention time point.