Background and aims: Patients with familial hypercholesterolaemia (FH) have an elevated risk of coronary heart disease (CHD). Here we compare changes in CHD mortality in patients with heterozygous (FH) pre 1992, before lipid-lowering therapy with statins was used routinely, and in the periods 1992–2008 and 2008–2016. Methods: 1903 Definite (DFH) and 1650 Possible (PFH) patients (51% women) aged 20–79 years, recruited from 21 lipid clinics in the United Kingdom and followed prospectively between 1980 and 2016 for 67,060 person-years. The CHD standardised mortality ratio (SMR) compared to the population in England and Wales was calculated (with 95% Confidence intervals). Results: There were 585 deaths, including 252 from CHD. Overall, the observed 2.4-fold excess coronary mortality for treated DFH post-1991 was significantly higher than the 1.78 excess for PFH (35% 95% CI 3%–76%). In patients with DFH and established coronary disease, there was a significant excess coronary mortality in all time periods, but in men it was reduced from a 4.83-fold excess (2.32–8.89) pre-1992 to 4.66 (3.46–6.14) in 1992–2008 and 2.51 (1.01–5.17) post-2008, while in women the corresponding values were 7.23 (2.65–15.73), 4.42 (2.70–6.82) and 6.34 (2.06–14.81). Primary prevention in men with DFH resulted in a progressive reduction in coronary mortality over the three time-periods, with no excess mortality evident post-2008 (0.89 (0.29–2.08)), although in women the excess persisted (post-2008 3.65 (1.75–6.72)). Conclusions: The results confirm the benefit of statin treatment in reducing CHD mortality, but suggest that FH patients with pre-existing CHD and women with FH may not be treated adequately.