<b><i>Background:</i></b> Characteristic changes in cerebral saturation (CrSO₂), amplitude-integrated electroencephalography (aEEG), and echocardiography (ECHO) may be associated with intraventricular hemorrhage (IVH); however, the feasibility of their combined application is not known. <b><i>Objective:</i></b> The aim of this work was to investigate the feasibility and safety of combined multimodal cerebral and hemodynamic monitoring in extremely low gestational age (ELGA) infants in the first 72 h after birth. <b><i>Methods:</i></b> In this prospective ­observational study of 50 infants born between 23 + 0 and 27 + 6 weeks gestation, we measured CrSO₂ and aEEG, starting &#x3c;8 h until 72 h of age. Sequential echocardiography and head ultrasound were performed at 4–8, 12–18, 24–30, and 48–60 h of age. The primary outcome was feasibility of multimodal monitoring, defined as &#x3e;75% of the subjects satisfying at least 3/4 criteria: (a) CrSO₂ and (b) aEEG monitoring each for &#x3e;75% of the time, and (c) at least 2 out of 4 ECHO and (d) head ultrasounds (at least one by age 24 h). Adverse reactions to sensors, desaturation, and bradycardia during ultrasound studies were recorded. <b><i>Results:</i></b> Fifty infants were enrolled over 14 months. Multimodal monitoring was feasible in 49 (98%) infants. Forty-one (82%) infants fulfilled all 4 criteria. Mild erythema below CrSO₂ sensors lasting 3–8 h without skin breakdown was noted in 8/50 subjects (16%). Desaturation was noted during 17/197 (8.6%) of the ultrasound studies. In total, 26/50 (52%) infants developed IVH (grade I/II, <i>n</i> = 22; grade III/IV, <i>n</i> = 4). <b><i>Conclusion:</i></b> Multimodal monitoring is feasible, safe, and well tolerated in ELGA infants in the first 72 h after birth.