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Background: Adequate perinatal management is essential in caring for extremely preterm (EP) infants. We aimed to evaluate and compare the impact of different protocols on short-term outcomes. Methods: A retrospective study was conducted on EP infants in a Romanian perinatal tertiary center during 2008–2012 and 2018–2022. Results: Data on 270 EP infants (121 in period I, 149 in period II) were analyzed collectively and stratified into two subgroups by gestational age. Initial FiO2 administration (100% vs. 40%% p < 0.001), lung recruitment at birth (19.0% vs. 55.7% p < 0.001), early rescue surfactant administration (34.7% vs. 65.8%; p < 0.001), and the mechanical ventilation rate (98.3% vs. 58.4%; p < 0.001) were significantly improved during period II. Survival rates of EP infants significantly improved from 41.3% to 72.5%, particularly in the 26–28 weeks subgroup (63.8% to 83%). Compared to period I, the overall frequency of severe IVH decreased in period II from 30.6% to 14.1%; also, BPD rates were lower (36.6% vs. 23.4%; p = 0.045) in the 26–28 weeks subgroup. Despite improvements, there were no significant differences in the frequencies of NEC, sepsis, PVL, ROP, or PDA. Conclusions: Implementing evidence-based clinical guidelines can improve short-term outcomes. [ABSTRACT FROM AUTHOR]