This study evaluated the relation between apolipoprotein B (apoB) decrease and coronary heart disease, stroke, and cardiovascular disease risk. Bayesian random-effects meta-analysis was used to evaluate the association of mean absolute apoB decrease (milligrams per deciliter) with relative risk of coronary heart disease (nonfatal myocardial infarction and coronary heart disease death), stroke (nonfatal stroke and fatal stroke), or cardiovascular disease (coronary heart disease, stroke, and coronary revascularization). Analysis included 25 trials (n = 131,134): 12 on statin, 4 on fibrate, 5 on niacin, 2 on simvastatin-ezetimibe, 1 on ileal bypass surgery, and 1 on aggressive versus standard low-density lipoprotein (LDL) cholesterol and blood pressure targets. Combining the 25 trials, each 10-mg/dl decrease in apoB was associated with a 9% decrease in coronary heart disease, no decrease in stroke, and a 6% decrease in major cardiovascular disease risk. Non-high-density lipoprotein (non-HDL) cholesterol decrease modestly outperformed apoB decrease for prediction of coronary heart disease (Bayes factor [BF] 1.45) and cardiovascular disease (BF 2.07) risk decrease; apoB decrease added to non-HDL cholesterol plus LDL cholesterol decrease slightly improved cardiovascular disease risk prediction (1.13) but did not improve coronary heart disease risk prediction (BF 1.03) and worsened stroke risk prediction (BF 0.83). In the 12 statin trials, apoB and non-HDL cholesterol decreases similarly predicted cardiovascular disease risk; apoB improved coronary heart disease prediction when added to non-HDL cholesterol/LDL cholesterol decrease (BF 3.33) but did not improve stroke risk prediction when added to non-HDL cholesterol/LDL cholesterol decrease (BF 1.06). In conclusion, across all drug classes, apoB decreases did not consistently improve risk prediction over LDL cholesterol and non-HDL cholesterol decreases. For statins, apoB decreases added information to LDL cholesterol and non-HDL cholesterol decreases for predicting coronary heart disease but not stroke or overall cardiovascular disease risk decrease.