Patients often adhere to intrathecal opioid therapy (IOT) for many years, despite the lack of scientific evidence for its efficacy and the scarce knowledge about long-term effects. Moreover, there is no knowledge on how the efficacy of IOT is influenced by cultural factors. We assessed the long-term efficacy and frequency of side effects of IOT in two culturally different patient samples. A chart review was conducted of all patients with IOT, who had been treated in interdisciplinary pain centers in Freiburg and in Tehran in a 15-year span. Personal data, diagnosis, duration of pain disease, pump type in use, revision operations, and opioid doses were recorded. Patients completed a questionnaire containing pain scores, pain-related disability (PDI), anxiety, depression, and unwanted side effects. Fourteen Iranian and 36 German patients (32 m/18 f) were studied. Mean duration of IOT was 10.2 years. Pain levels prior to IOT were 7.64 (NRS) (range 4-10, SD 1.64), 3.86 (range 0-9, SD 2.32) directly after pump implantation, and 4.17 (range 0-10, SD 2.11) at time of follow-up. Iranian patients had significantly lower pain levels directly after implantation, depression scores, and pain-related disability. Frequent side effects were obstipation, sexual dysfunction, urinary retention, and fatigue. Most side effects were significantly less frequent in the Iranian sample. There were no severe complications or permanent neurological deficit. Our study demonstrates the effectiveness of IOT also for long-term application. Differences in clinical efficacy are partially due to cultural factors. Side effects are frequent but not limiting patient satisfaction.