Preclinical evidence suggests that time-restricted eating (TRE) exerts beneficial metabolic and cardiovascular effects by ameliorating inflammation and modulating immune cell function. However, the effect in patients with established coronary artery disease remains unknown. In this prospective, randomized, open-label, blinded end point crossover study, we explored the effect of a 2-week TRE intervention (eating allowed between 8 am and 2 pm) on metabolomic parameters, innate immune cell function, and systemic inflammation in patients with a history of myocardial infarction. Patients were randomized to a 2-week TRE intervention or a 2-week control period with their regular diet, followed by a ≥6-week washout and crossover to the other group. Blood samples were collected in a fasted state before and after each period. In total, 19 patients (mean age, 65.3 years [SD 8.1], 2 [11%] female), of whom 10 were randomized to start with the control diet, and 9 randomized to start with the TRE diet, were included in the current analysis. All visits were conducted between November 2022 and January 2024. Compared with the control diet, the TRE diet led to reduced neutrophil counts, lower neutrophil-to-lymphocyte ratio, decreased neutrophil CD11b expression, and anti-inflammatory changes in the monocyte transcriptome. Furthermore, a reduction in low-grade systemic inflammation was found. The TRE diet was associated with widespread metabolic changes. No significant effects on monocyte subsets, monocyte inflammatory surface marker expression, or cytokine production capacity were observed. Our findings highlight the capability of TRE in the modulation of inflammation, suggesting a potential role in reducing cardiovascular risk in patients with established cardiovascular disease.