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Background: The aim in this study was to investigate the effect of vitamin D (25(OH)D3) supplementation on heat shock protein 60 (HSP 60) and other inflammatory markers (IL-17, TNF-α, PAB) in patients with coronary heart disease (CHD). Methods: In this double-blind, randomized clinical trial, we recruited 80 male and female patients aged 30–60 with CHD and 25(OH)D3 serum levels < 30 ng/ml from Rasool-e-Akram Hospital in Tehran, Iran. Serum levels of HSP 60 as primary outcome, and 25(OH)D3, IL-17, TNF-α, PAB, lipid profiles and parathyroid hormone (PTH) as secondary outcomes were measured at baseline and post-intervention. We randomly assigned eligible participants to a placebo group ( N = 40) or an intervention group (N = 40) (50,000 IU/wk. vitamin D supplement) for eight weeks. Results: The results demonstrated that vitamin D supplementation resulted in a significant increase in 25(OH) D3 serum levels in the intervention group compared to the placebo group (46.86 vs. 7.28 ng/ml). PTH levels decreased in the intervention group compared to the placebo group (− 19.81 vs. 2.92 pg/ml) after eight weeks of supplementation. Furthermore, we observed a significant change in waist circumference (− 0.97 vs. -0.26 cm), fat percentage (−.13 vs. 0.1%), systolic blood pressure (− 3.85 vs. -2.11 mmHg) and diastolic blood presure (− 4 vs. -1.86 mmHg) in the vitamin D group compared to the placebo group (all P values < 0.05). Other variables did not significantly change after the intervention. Conclusion: Based on our findings, weekly vitamin D supplementation of 50,000 IU for eight weeks in patients with CHD resulted in decreased systolic and diastolic blood pressure, waist circumference and fat percentage. No significant effect on HSP 60, inflammatory markers or lipid profiles was observed. Trial registration: IRCT, IRCT201612122365N14. Registered 12 December 2016. [ABSTRACT FROM AUTHOR]