Background: Oligometastatic breast cancer (OMBC) is a clinical entity with favorable prognosis compared to MBC in general, but the optimal treatment for individual patients remains unclear. We compared high dose chemotherapy (HDCT) to conventional dose chemotherapy (CDCT) in patients receiving local ablative therapy (LAT) of all disease sites in HER2-negative OMBC that harbors homologous recombination deficiency (HRD). Methods: In this open-label phase 3 study, we randomly assigned patients with OMBC after 3 cycles of induction CDCT to either continue with CDCT (up to a maximum total of 8 cycles) or switch to HDCT. OMBC was defined as 1-3 distant metastatic lesions, with or without locoregional disease, all amenable to LAT. Main eligibility criteria included pathologic proof of a distant metastatic lesion, HRD (based on either germline BRCA1/2 mutation and/or a BRCA-like profile in the tumor), and a favorable response to induction CDCT. The primary endpoint was event-free survival (EFS), defined as time since randomization to recurrence or death. Overall survival (OS), safety and quality of life (QoL) were key secondary endpoints. Following the advice of the independent data monitoring committee, analyses were performed before the prespecified number of events was reached. Results: Between November 2012 and May 2022, 36 patients were allocated to HDCT and 39 to CDCT. 52 (69%) tumors were triple negative and 23 (31%) were hormone receptor positive; 39 patients (52%) had a solitary metastasis and 43 (57%) had synchronous OMBC. After a median follow-up of 52 months (interquartile range 28-97), 42 EFS-events had occurred. Median EFS in the HDCT-group was 28 months (95% CI 21 – not reached (NR)) compared to 25 months (95% CI 14 – NR) in the CDCT-group (hazard ratio (HR) 0.78 (95% CI 0.42 – 1.42, p = 0.411). Median OS was 67 months (95% CI 37 – NR) in the HDCT-group versus 36 months (95% CI 26 – NR) in the CDCT-group (HR 0.74, 95% CI 0.37 – 1.48, p = 0.398). 5-year EFS was 40% and 30%, and 5-year OS was 51% and 49% in the HDCT- and CDCT-group, respectively. 34 (94%) patients in the HDCT-group experienced grade 3 or higher adverse events, compared to 25 (64%) patients in the CDCT-group; no grade 5 adverse events occurred. QoL was comparable between groups at 12 months. Conclusions: HDCT does not improve outcome compared to CDCT in patients with OMBC harboring HRD and can therefore not be recommended. Survival in this highly selected group of patients with OMBC, all receiving LAT, compares favorably to survival in the overall MBC population. The optimal systemic therapy for patients with OMBC requires further study. Clinical trial information: NCT01646034.