Background and aims: Amphetamines are the second most commonly used class of illicit drugs. We aimed to produce pooled estimates of mortality risks among people with regular or dependent use of amphetamines, with a focus upon all-cause mortality as well as specific causes of death. Design: Systematic review and meta-analysis of cohorts of people with problematic use or dependence on amphetamines with data on all-cause or cause-specific mortality. Setting and participants: Of 4240 papers, 30 were eligible, reporting on 25 cohorts that measured all-cause mortality, drug poisoning, suicide, accidental injuries, homicide and cardiovascular mortality. Cohorts (n = 35-74 139) were in North America, several Nordic countries and Asia Pacific. Measurement: Titles/abstracts were independently screened by one reviewer and excluded those reviewed by a second reviewer. Full-text screening was by two reviewers with discrepancies resolved via a third reviewer. We extracted data on crude mortality rates (CMR) per 100 person-years (py), standardized mortality ratios (SMRs). We imputed SMRs where possible if not reported by study authors. We also calculated mortality relative risks. Data were pooled using random-effects models; potential reasons for heterogeneity were explored using subgroup analyses and meta-regressions. Findings: Twenty-three cohorts contributed data for the pooled all-cause CMR: 1.14 per 100 py [95% confidence interval (CI) = 0.92-1.42]. Pooled cause-specific mortality rates were: drug poisoning, 0.14 per 100 py (95% CI = 0.06-0.34); cardiovascular disease, 0.13 per 100 py (95% CI = 0.06-0.29); suicide, 0.20 per 100 py (95% CI = 0.07-0.55); accidental injury, 0.20 per 100 py (95% CI = 0.08-0.47) and homicide, 0.03 per 100 py (95% CI = 0.02-0.06). There was substantial heterogeneity for all pooled CMR estimates except homicide. The pooled all-cause SMR was 6.83 (95% CI = 5.27-8.84). Pooled cause-specific SMRS were: poisoning, 24.70 (95% CI = 16.67, 36.58); homicide, 11.90 (95% CI = 7.82-18.12); suicide, 12.20 (95% CI = 4.89-30.47); cardiovascular disease, 5.12 (95% CI = 3.74-7.00) and accidental injury, 5.12 (95% CI = 2.88-9.08). Conclusions: People with regular or dependent amphetamine use are at elevated risk of a range of causes of mortality compared with people without regular or dependent amphetamine use.