The availability of long-term (>2 years) safety outcomes of spinal cord stimulation (SCS) remains limited. We evaluated safety in a global SCS registry for chronic pain. Participants were prospectively enrolled globally at 79 implanting centers and followed out to 3 years after device implantation. Of 1881 participants enrolled, 1289 received a permanent SCS implant (1776 completed trial). The annualized rate of device explant was 3.5% (all causes), and 1.1% due to inadequate pain relief. Total incidence of device explantation >3 years was 7.6% (n = 98). Of these, 32 subjects (2.5%) indicated inadequate pain relief as cause for removal. Implant site infection (11 events) was the most common device-related serious adverse event (<1%). This prospective, global, real-world study demonstrates a high-level of safety for SCS with low rate of explant/serious adverse events. : NCT01719055 (ClinicalTrials.gov).