This study is an evaluation of prescription opioid use on the island of La Gomera, a mainly rural area, during the period 2016–2019 at various levels. Data were extracted from the wholesalers who supply the community pharmacies at the population level. Prescription opioid use was measured as defined daily doses per 1,000 inhabitants/day (DID) and by the number of units sold per 1,000 inhabitants and year (units sold). This provided an island total of La Gomera’s overall prescription of opioids and its rate of change, as well as differences in prescribing at the municipal and health area level. Tramadol with acetaminophen and tramadol in monotherapy were the most consumed by “units sold” parameter, which accounted for 69.48% and 18.59% of the total. The situation was similar for DID, although with lower percentages, but a significant increase was observed in the use of fentanyl and buprenorphine, around 15% in each case. The balance between the uses of weak or strong opioids was different in La Gomera compared to that of Spain as a whole. In Spain, almost 70% of the prescriptions were for weak opioids compared to 58.67% in La Gomera. Fentanyl was the most used strong opioid (16.10%) followed by tapentadol and buprenorphine, around 5% each, whereas in La Gomera, buprenorphine was the most consumed (15.75%) followed by fentanyl (14.87%) and tapentadol (5.82%). These differences in prescription opioid use are most likely explained by prescriber characteristics, whereas the population age, socioeconomic status, or living in rural/urban area are not decisive determinants.