The aim of this prospective cohort study was to evaluate the effect of compression garments under resting conditions and after the induction of delayed-onset muscle soreness (DOMS) by MR perfusion imaging using intravoxel incoherent motion (IVIM). Magnetic resonance imaging of both lower legs of 16 volunteers was performed before and after standardized eccentric exercises that induced DOMS. A compression garment (21-22 mmHg) was worn during and for 6 h after exercise on one randomly selected leg. IVIM MR imaging, represented as total muscle perfusion D*f, perfusion fraction f and tissue diffusivity D, were compared between baseline and directly, 30 min, 6 h and 48 h after exhausting exercise with and without compression. Creatine kinase levels and T2-weighted images were acquired at baseline and after 48 h. DOMS was induced in the medial head of the gastrocnemius muscle (MGM) in all volunteers. Compression garments did not show any significant effect on IVIM perfusion parameters at any time point in the MGM or the tibialis anterior muscle (p > 0.05). Microvascular perfusion in the MGM increased significantly in both the compressed and noncompressed leg between baseline measurements and those taken directly after and 30 min after the exercise: the relative median f increased by 31.5% and 24.7% in the compressed and noncompressed leg, respectively, directly after the exercise compared with the baseline value. No significant change in tissue perfusion occurred 48 h after the induction of DOMS compared with baseline. It was concluded that compression garments (21-22 mmHg) do not alter microvascular muscle perfusion at rest, nor do they have any significant Abbreviations used: C, compressed; CK, creatine kinase; DOMS, delayed-onset muscle soreness; EIMD, exercise-induced muscle damage; IFCC, International Federation of Clinical Chemistry and Laboratory Medicine; IVIM, intravoxel incoherent motion; MGM, medial head of the gastrocnemius muscle; NC, noncompressed; NEX, number of excitations; ROI, region of interest; SPAIR, spectral attenuated inversion recovery; TA, tibialis anterior muscle; TE, echo time; TIRM, turbo inversion recovery magnitude; TR, repetition time.