<b><i>Background:</i></b> Fatal opioid overdose is a significant public health problem with increasing incidence in developed countries. This study aimed to describe demographic and service user characteristics of decedents of opioid overdose in Wales to identify possible targets for behaviour modification and life-saving interventions. <b><i>Methods:</i></b> A retrospective cross-sectional analysis was conducted of a census sample of opioid overdose-related deaths recorded between January 01, 2012, and October 11, 2018, in Wales. UK Office for National Statistics, Welsh Demographic Service, and National Health Service datasets were linked deterministically. Decedents’ circumstances of death, demographic characteristics, residency, and health service use were characterized over 3 years prior to fatal overdose using descriptive statistics. <b><i>Results:</i></b> In total, 638 people died of opioid overdose in Wales between January 01, 2012, and October 11, 2018, with an incidence rate of 3.04 per 100,000 people per year. Decedents were predominantly male (73%) and middle aged (median age 50 years). Fatal overdoses predominantly occurred in the community (93%) secondary to heroin (30%) or oxycodone derivative use (34%). In the 3 years prior to death, decedents changed address frequently (53%) but rarely moved far geographically. The majority of decedents had recently visited the emergency department (83%) or were admitted to the hospital (64%) prior to death. Only a minority had visited specialist drug services (32%). <b><i>Conclusions:</i></b> Deaths from opioid overdose typically occur in middle-aged men living peripatetic lifestyles. Victims infrequently visit specialist drug services but often attend emergency medical services. Emergency department-based interventions may therefore be important in prevention of opioid overdose fatalities in the community.