Previous reviews of PCSK9 inhibitor trials are limited by a focus on composite cardiovascular outcomes. ClinicalTrials.gov provides trial results for individual clinical outcomes. Aim of this systematic review was to assess the effect of PCSK9 inhibitors on the risk of myocardial infarction, stroke/TIA, heart failure, diabetes mellitus, neurocognitive events, all-cause serious adverse events (SAE), and all-cause deaths as registered on ClinicalTrials.gov. PubMed, regulatory reports, ClinicalTrials.gov, and company websites were used to search studies. Randomized trials comparing PCSK9 inhibitor with placebo in participants with hypercholesterolemia were eligible. Study characteristics, risk of bias, and numbers of participants with the outcomes of interest were collected. We identified 33 lipid-lowering and 4 clinical outcomes trials with results on ClinicalTrials.gov (n = 16,958 and n = 73,836, respectively). Risk of bias was generally high. PCSK9 inhibitors did not affect the risk of any of the investigated outcomes in either type of trial. However, in clinical outcomes studies, alirocumab decreased the risk of all-cause SAE (OR 0.92; 95% CI 0.86–0.98), and evolocumab probably increased the risk of mortality (OR 1.12; 95% CI 1.00–1.25). Our meta-analysis of clinical events registered on ClinicalTrials.gov did not show that PCSK9 inhibitors improve cardiovascular health. Evolocumab increased the risk of all-cause mortality.