Objectives: To evaluate the optimal lipid to measure in monitoring patients, we assessed three factors that influence the choice of monitoring tests: (1) clinical validity; (2) responsiveness to therapy changes and (3) the size of the long-term 'signal-to-noise' ratio. Design: Longitudinal analyses of repeated lipid measurement over 5 years. Setting: Subsidiary analysis of a Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study - a clinical trial in Australia, New Zealand and Finland. Participants: 9014 patients aged 31-75 years with previous acute coronary syndromes. Interventions: Patients were randomly assigned to 40 mg daily pravastatin or placebo. Primary and secondary outcome measures: We used data on serial lipid measurements - at randomisation, 6 months and 12 months, and then annually to 5 years - of total cholesterol; low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and their ratios; triglycerides; and apolipoproteins A and B and their ratio and their ability to predict coronary events. Results: All the lipid measures were statistically significantly associated with future coronary events, but the associations between each of the three ratio measures (total or LDL cholesterol to HDL cholesterol, and apolipoprotein B to apolipoprotein A1) and the time to a coronary event were better than those for any of the single lipid measures. The two cholesterol ratios also ranked highly for the long-term signal-to-noise ratios. However, LDL cholesterol and non - HDL cholesterol showed the most responsiveness to treatment change. Conclusions: Lipid monitoring is increasingly common, but current guidelines vary. No single measure was best on all three criteria. Total cholesterol did not rank highly on any single criterion. However, measurements based on cholesterol subfractions-non-HDL cholesterol (total cholesterol minus HDL cholesterol) and the two ratios - appeared superior to total cholesterol or any of the apolipoprotein options. Guidelines should consider using non-HDL cholesterol or a ratio measure for initial treatment decisions and subsequent monitoring.