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Objective: To test the effect of long‐term pegfilgrastim on collateral function and myocardial ischaemia in patients with chronic stable coronary artery disease (CAD). Methods: This was a prospective clinical trial with randomized 2:1 allocation to pegfilgrastim or placebo for 6 months. The primary study endpoint was collateral flow index (CFI) as obtained during a 1‐minute ostial coronary artery balloon occlusion. CFI is the ratio of mean coronary occlusive divided by mean aortic pressure both subtracted by central venous pressure (mm Hg/mm Hg). Secondary endpoints were signs of myocardial ischaemia determined during the same coronary occlusion, that is quantitative intracoronary (i.c.) ECG ST‐segment shift (mV) and the occurrence of angina pectoris. Endpoints were obtained at baseline before and at follow‐up after three subcutaneous study drug injections. Results: Collateral flow index in the pegfilgrastim group changed from 0.096 ± 0.076 at baseline to 0.126 ± 0.070 at follow‐up (P = 0.0039), while in the placebo group CFI changed from 0.157 ± 0.146 to 0.122 ± 0.043, respectively (P = 0.29); the CFI increment at follow‐up was +0.030 ± 0.075 in the pegfilgrastim group and −0.034 ± 0.148 in the placebo group (P = 0.0172). In the pegfilgrastim group, i.c. ECG ST‐segment shift changed from +1.23 ± 1.01 mV at baseline to +0.93 ± 0.97 mV at follow‐up (P = 0.0049), and in the placebo group, it changed from +0.98 ± 1.02 mV to +1.43 ± 1.09 mV, respectively (P = 0.05). At follow‐up, the fraction of patients free from angina pectoris during coronary occlusion had increased in the pegfilgrastim but not in the placebo group. Conclusion: Pegfilgrastim given over the course of 6 months improves collateral function in chronic stable CAD, which is reflected by reduced myocardial ischaemia during a controlled coronary occlusion. [ABSTRACT FROM AUTHOR]