Purpose : The effectiveness of an opioid rotation to parenteral hydromorphone in advanced cancer patients has never been investigated. Therefore, the purpose of this study was to investigate the analgesic efficacy and side effects of parenteral hydromorphone on serious cancer-related pain. ; Methods : We included 104 consecutive advanced cancer patients who were extensively pretreated with opioids. They were rotated to parenteral hydromorphone because they failed to achieve adequate pain relief on other opioids. Pain intensity and side effects were daily assessed. The moment of adequate pain control was defined as the first of at least 2 consecutive days when the mean pain intensity at rest was ≤4 (on a 0–10 numeric rating scale) and side effects were tolerable. ; Results : The reasons for rotation to parenteral hydromorphone were inadequate pain control with/without expected delivery problems due to high opioid dosages (n = 61) and intolerable side effects with persistent pain (n = 43). Adequate pain control was achieved in 86 patients (83%) within a mean of 5 days. Eight of 86 patients still had side effects, but these were scored as acceptable. The mean pain intensity at rest decreased from 5.4 [standard deviation (sd) = 2.1] to 2.4 (sd = 1.5; p