Background People with HIV (PWH) have increased cardiovascular risk. Higher leukocyte count has been associated with coronary artery disease (CAD) events in the general population. It is unknown whether the leukocyte-CAD association also applies to PWH. Methods In a case-control study nested within the Swiss HIV Cohort Study, we obtained uni- and multivariable odds ratios (OR) for CAD events, based on traditional and HIV-related CAD risk factors, leukocyte count, and confounders previously associated with leukocyte count. Results We included 536 cases with a first CAD event (2000-2021; median age 56 years, 87% male, 84% with suppressed HIV-RNA) and 1464 event-free controls. Cases had higher latest leukocyte count prior to CAD event than controls (median [interquartile range], 6495 [5300-7995] vs. 5900 [4910-7200]; p < 0.01), but leukocytosis (>11000/uL) was uncommon (4.3% vs. 2.1%; p = 0.01). In the highest vs. lowest leukocyte quintile at latest time point prior to CAD event, participants had univariable CAD-OR = 2.27 (95% confidence interval, 1.63-3.15) and multivariable adjusted CAD-OR = 1.59 (1.09-2.30). For comparison, univariable CAD-OR for dyslipidemia, diabetes, and recent abacavir exposure were 1.58 (1.29-1.93), 2.19 (1.59-3.03), and 1.73 (1.37-2.17), respectively. Smoking and, to a lesser degree, alcohol and ethnicity attenuated the leukocyte-CAD association. Leukocytes measured up to 8 years pre-event were significantly associated with CAD events. Conclusions PWH in Switzerland with higher leukocyte counts have an independently increased risk of CAD events, to a degree similar to traditional and HIV-related risk factors.