Introduction Peru is among the top ten countries with the highest number of coronavirus disease 2019 (COVID-19) cases worldwide. The aim of the study was to describe the clinical features of hospitalized adult patients with COVID-19 and to determine the prognostic factors associated with in-hospital mortality. Methods We conducted a retrospective cohort study among adult patients with COVID-19 admitted to Hospital Cayetano Heredia; a tertiary care hospital in Lima, Peru. The primary outcome was in-hospital mortality. Multivariate Cox proportional hazards regression was used to identify factors independently associated with in-hospital mortality. Results A total of 369 patients (median age 59 years [IQR:49-68]; 241 (65.31%) male) were included. Most patients (68.56%) reported at least one comorbidity; more frequently: obesity (42.55%), diabetes mellitus (21.95%), and hypertension (21.68%). The median duration of symptoms prior to hospital admission was 7 days (IQR: 5-10). Reported in-hospital mortality was 49.59%. By multiple Cox regression, oxygen saturation (SaO2) values of less than 90% on admission correlated with mortality, presenting 1.86 (95%CI: 1.02-3.39), 4.44 (95%CI: 2.46-8.02) and 7.74 (95%CI: 4.54-13.19) times greater risk of death for SaO2 of 89-85%, 84-80% and <80%, respectively, when compared to patients with SaO2 >90%. Additionally, age >60 years was associated with 1.88 times greater mortality. Conclusions Oxygen saturation below 90% on admission is a strong predictor of in-hospital mortality in patients with COVID-19. In settings with limited resources, efforts to reduce mortality in COVID-19 should focus on early identification of hypoxemia and timely access to hospital care.