Background: The purpose of this randomized trial was to compare a personally-tailored symptom management intervention consisting of 4 automated telephone assessments and tailored education for improving symptom self-management among prostate cancer survivors to usual care (1 non-tailored newsletter about symptom management). We hypothesized improved symptom self-management and prostate cancer quality of life following the intervention. Methods: A total of 556 prostate cancer survivors experiencing symptom burden were recruited from April 2015 to February 2017 across 4 sites. Participants were randomized to intervention (n = 278) and usual care (n = 278) groups as reported in our protocol. Our primary outcome was symptom burden assessed via patient report 5 months after enrollment using the EPIC-26 instrument. Secondary outcomes included psychosocial outcomes and domain-specific changes according to intervention participants’ primary symptom area (urinary, bowel, sexual, general). We used multivariable regression analysis to evaluate intervention impact on outcomes. Results: The mean age of prostate cancer survivors was 66.7 years and the majority was treated with radiation therapy (56.7% vs. 46.2% surgery). The 5 month primary outcome assessment was completed by 89% of participants. There were no baseline differences across groups. At 5 months, we observed differences between groups in urinary domains (irritative - 61.8 control vs. 63.4 intervention, adjusted mean difference (aMD) 2.6, p = 0.07; obstructive - 74.5 control vs. 77.4 intervention, aMD 2.6, p = 0.07) with no significant differences in other outcomes. Intervention participants choosing urinary (crude mean difference (cMD) irritative 3.0; p = 0.09, obstructive 6.1; p < 0.01), bowel (cMD 9.1; p = 0.08), and sexual (cMD 5.6; p < 0.01) domains as their primary focus area reported improvements at 5 months. Participants reported high satisfaction with the intervention. Conclusions: A personally-tailored, automated telephone symptom management intervention for prostate cancer survivors was feasible and led to differences in urinary and sexual health symptoms in this randomized trial. Self-management of treatment-related side effects appears warranted. Clinical trial information: NCT01900561