OBJECTIVE Development of a save and effective protocol for analgosedation of patients undergoing painful interventional procedures. METHODS In a prospective trial a consecutive series of 72 adult patients underwent analgosedation during painful interventions. A radiologist performed the analgosedation, the patients received a combination of a shortly effective piperidine derivative (Alfentanil [Rapifen(R)]; 7.5 - 15 microgram/kg body weight) and Benzodiazepine (midazolam [Dormicum(R)]; 20 microgram/kg body weight). After pre-procedure oxygenation patients were continuously monitored. Pain and discomfort were scored using an established visual-analog pain score (0 - 10). A control group (n = 24) had received midazolam, pentazocine or fentanyl according to the study protocol. RESULTS All procedures could be carried out by an interventional radiologist and a nurse and/or technologist only. In 69/72 cases adequate analgosedation could be achieved. Injection of alfentanil was titrated, with a rapid onset and short acting effect of the analgesia. Patients reported an average pain score of 2.6 vs. 4.5 in the control group. Over 55 % experienced no or mild pain (score 0 - 3), in the control group only 8 % reached this level. CONCLUSIONS A combination of shortly effective alfentanil and midazolam allows interventional radiologists to perform major procedures alone under effective analgosedation. This medication scheme is superior to the medication upon demand.