ObjectivesTo review the metrics and findings of studies evaluating effects of drug decriminalisation or legal regulation on drug availability, use or related health and social harms globally.DesignSystematic review with narrative synthesis.Data sourcesWe searched MEDLINE, Embase, PsycINFO, Web of Science and six additional databases for publications from 1 January 1970 through 4 October 2018.Inclusion criteriaPeer-reviewed articles or published abstracts in any language with quantitative data on drug availability, use or related health and social harms collected before and after implementation of de jure drug decriminalisation or legal regulation.Data extraction and synthesisTwo independent reviewers screened titles, abstracts and articles for inclusion. Extraction and quality appraisal (modified Downs and Black checklist) were performed by one reviewer and checked by a second, with discrepancies resolved by a third. We coded study-level outcome measures into metric groupings and categorised the estimated direction of association between the legal change and outcomes of interest.ResultsWe screened 4860 titles and 221 full-texts and included 114 articles. Most (n=104, 91.2%) were from the USA, evaluated cannabis reform (n=109, 95.6%) and focussed on legal regulation (n=96, 84.2%). 224 study outcome measures were categorised into 32 metrics, most commonly prevalence (39.5% of studies), frequency (14.0%) or perceived harmfulness (10.5%) of use of the decriminalised or regulated drug; or use of tobacco, alcohol or other drugs (12.3%). Across all substance use metrics, legal reform was most often not associated with changes in use.ConclusionsStudies evaluating drug decriminalisation and legal regulation are concentrated in the USA and on cannabis legalisation. Despite the range of outcomes potentially impacted by drug law reform, extant research is narrowly focussed, with a particular emphasis on the prevalence of use. Metrics in drug law reform evaluations require improved alignment with relevant health and social outcomes.