Purpose The present study summarizes the first experience with 177Lu-PSMA-617 (177Lu-PSMA) treatment in metastatic castration-resistant prostate cancer (PCa) in our institution. Methods This was an analysis of the first 30 consecutive patients who underwent 177Lu-PSMA therapy. Biochemical response was defined as prostate-specific antigen decrease of 50% or greater. Clinical toxicity was based on standardized physician's report, and biochemical and hematological toxicity was graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) criteria. Clinical response was objectified in terms of severity of pain and usage of analgesics after separate treatment cycles. Results Thirty patients with advanced PCa received therapy cycles with 6 GBq 177Lu-PSMA (median, 4; range, 1-6). After the first cycle, usage of analgesics decreased in 45% of the patients. During treatment, maximum prostate-specific antigen decrease was 50% or greater and 90% or greater in 57% and 24% of the patients, respectively. Despite CTCAE grades III and IV anemia occurring in 2 patients (7%), all other newly originated biochemical toxicity was limited to maximum CTCAE grades I and II. Grade II xerostomia occurred in 17% of the patients. During a median follow-up length of 13.7 months (range, 9.8-32.3 months), median overall survival from start of the first therapy cycle was 11.3 months (range, 1.4-32.3 months). Conclusions These results confirm the favorable safety and efficacy profile of 177Lu-PSMA, even up to 6 treatment cycles. Therefore, 177Lu-PSMA seems a promising therapeutic strategy for metastatic castration-resistant PCa patients. However, randomized controlled trials are warranted to obtain robust data.