Objectives To describe and assess clinical characteristics and factors associated with mortality in adult patients with COVID-19 admitted to a national referral hospital in Peru. Methods We conducted a prospective cohort study that included hospitalized patients older than 18 years with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis. Patients with a positive rapid serological test on admission but no respiratory symptoms nor compatible images were excluded. We collected the data from clinical records. Results A total of 813 adults were included, 544 (66.9%) with confirmed COVID-19. The mean age was 61.2 years (standard deviation: 15.0), and 575 (70.5%) were male. The most frequent comorbidities were hypertension (34.1%) and obesity (25.9%). On admission, the most frequent symptoms were dyspnea (82.2%) and cough (53.9%). A total of 114 (14.0%) patients received mechanical ventilation, 38 (4.7%) were admitted to the intensive care unit, and 377 (46.4%) died. The requirement for ventilatory support, greater lung involvement, and inflammatory markers were associated with higher mortality. It was found that for every 10-year age increase, the risk of dying increased 32% (relative risk: 1.32; 95% confidence interval: 1.25 to 1.38). Those who were admitted to the intensive care unit and and were placed on mechanical ventilation had 1.39 (95% confidence interval: 1.13 to 1.69) and 1.97 (95% confidence interval: 1.69 to 2.29) times the risk of dying compared to those who did not, respectively. Conclusion We found a high mortality rate among hospitalized patients associated with older age, higher inflammatory markers, and greater lung involvement.