Acknowledgement of the prevalence of recreational opioid use (PROU) is key to the planning and evaluation of care services. However, in Spain, the prevalence of PROU in recent years is unknown. The objective of this study was to estimate the PROU between 2005 and 2019 in the general populations of six Spanish cities. A benchmark-multiplier methodology was used to estimate the PROU population size. The benchmark used was overdose deaths from recreational opioid use in Spain’s six most populated cities. The multiplier was the overdose death rate in a cohort of heroin users. Linear regression was used to estimate the trend of the PROU estimate over the set period of years. In 2005, the PROU was 4.78 (95%CI 3.16–7.91) per 1000 people. The estimated trend decreased, with the two lowest values being 2.35 per 1000 in 2015 and 2.29 in 2018. In 2019 the PROU was 2.60 per 1000 (95%CI 1.72–4.31), 45% lower than in 2005. While the decline in the PROU continues, its deceleration over the last four years calls for increased vigilance, especially in light of the opioid crisis in North America that has occurred over the last few years.