Coronavirus 2019 disease (COVID-19) continues to challenge healthcare systems globally as many countries are currently experiencing an increase in the morbidity and mortality. Compare baseline characteristics, clinical presentation, treatments, and clinical outcomes of patients admitted during the second peak to those admitted during the first peak. Retrospective analysis of 258 COVID-19 patients consecutively admitted to the Tel Aviv Medical Center, of which, 131 during the first peak (March 21-May 30, 2020) and 127 during the second peak (May 31-July 16, 2020). First and second peak patients did not differ in baseline characteristics and clinical presentation at admission. Treatment with dexamethasone, full-dose anticoagulation, tocilizumab, remdesivir, and convalescent plasma transfusion were significantly more frequent during the second peak, as well as regimens combining 3-4 COVID-19-directed drugs. Compared to the first peak, 30-day mortality and invasive mechanical ventilation rates as well as adjusted risk were significantly lower during the second peak (10.2%, vs 19.8% vs p = 0.028, adjusted HR 0.39, 95% CI 0.19-0.79, p = 0.009 and 8.8% vs 19.3%, p = 0.002, adjusted HR 0.29, 95% CI 0.13-0.64, p = 0.002; respectively). Rates of 30-day mortality and invasive mechanical ventilation, as well as adjusted risks, were lower in the second peak of the COVID-19 pandemic among hospitalized patients. The change in treatment strategy and the experienced gained during the first peak may have contributed to the improved outcomes.