Background: Docetaxel is first line chemotherapy in CRPC. Re-188 is a beta-emitting radiopharmaceutical that targets bone metastases. We investigated whether treatment with docetaxel plus Re-188 improved efficacy of first line chemotherapy. Methods: Patients with progressive CRPC and osteoblastic bone metastases were randomized for first line docetaxel 75 mg/m² 3-weekly plus prednisone with or without 2 injections of Re-188 after the 3^rd (40 MBq/kg) and after the 6^th (20 MBq/kg) cycle of docetaxel. Primary endpoint was progression free survival (PFS), a composite endpoint of either PSA, radiographic or clinical progression. 88 men were included to detect a targeted improvement of PFS at 6 months from 60% in the control group to 75% in the experimental group (power 77%; one-sided significance level 0.05; considered drop-out rate 10%). Patients were stratified by extent of bone metastases and hospital. Results: 42 patients received standard treatment and 46 patients combination therapy. Median number of cycles of docetaxel was 9 in the control group and 8 in the experimental group. Median follow up was 18.4 months. Two patients from the experimental group did not start treatment after randomization but intention to treat analysis was performed. No differences in PFS, survival and PSA became apparent between the two groups. In general pain responses were comparable, but musculoskeletal pain was reported less frequently in the combination group compared to control (88% versus 68%; p 0.024). Neutropenia grade 3/4 was more often seen in the combination group (16%) than in the control group (5%), but no differences in neutropenic fever (16% vs 14% respectively). Conclusions: Combined treatment with Re-188 and docetaxel is safe and feasible but does not improve PFS in patients with CRPC. However incidence of musculoskeletal pain was lower with combination therapy.