Quality use of anti-hypertensives and cholesterol-lowering medications is crucial for successful cardiovascular disease management. This systematic review aimed to estimate levels of over and underuse of services for primary and secondary prevention of cardiovascular diseases from 2000 to 2020: overprescribing/underprescribing, overtesting/undertesting and overutilisation/ underutilisation of procedures compared to clinical practice guideline recommendations. Thirteen studies from USA, Europe, Asia and Australia were included. Wide practice variation was identified. Six studies reported overuse (e.g. perioperative cardiac consultations, anti-hypertensive overprescribing for normotensive or pre-hypertensive people); and ten studies reported underuse (e.g. under-prescribing of statins when indicated and under-screening for familial hypercholesterolemia). Lifestyle recommendations for cardiovascular disease prevention were largely underused. In summary, lack of adherence to published guidelines was prevalent over the past two decades for both primary and secondary prevention across settings. Further investigation of potentially justifiable deviations from guidelines are warranted to verify the estimates and identify points for intervention.