Background Treatment options for cluster headache (CH) include acute, transitional and prophylactic strategies. We assessed the efficacy and safety of a single occipital nerve block (ONB) in patients with episodic (eCH) and chronic CH (cCH). Methods In this prospective, observational study 101 CH were treated with a single ONB using triamcinolone 10 mg and bupivacaine. Attack frequency, pain intensity and side effects were assessed at days 1 and 7 after ONB and thereafter weekly for 60 days until recurrence of attacks. Results Baseline mean daily attack frequency was 2.9 ± 2.5 (eCH) and 3.3 ± 2.9 (cCH), which was reduced to 0.7 ± 1.2 (eCH) and 1.1 ± 1.4 (cCH) after one day ( p = 0.08 for group difference) and to 1.1 ± 1.6 (eCH) and 1.9 ± 2.3 (cCH) after seven days ( p = 0.01 for group difference). In patients with eCH the pain-free period lasted longer compared to cCH ( p = 0.004). There was no association between the presence of local anesthesia and treatment response ( p = 0.88). No serious adverse events occurred. Conclusion ONB is an easy, safe and effective transitional treatment option in case of insufficient response of CH to treatment both in patients with eCH and cCH. Patients with eCH have a better and more sustainable treatment response.