Objective: To describe mortality of in-hospital patients with COVID-19 and compare risk factors between survivors and non-survivors. Design: Prospective cohort of adult inpatients. Setting: Tertiary healthcare teaching hospital in Guadalajara, Mexico. Participants: All patients with confirmed COVID-19 hospitalised from 25 March to 7 September 2020 were included. End of study: 7 November 2020. Primary outcome measures: Patient survival analysed by the Kaplan-Meier method and comparison of factors by the log-rank test. Mortality risk factors analysed by multivariate Cox's proportional-hazard model. Results: One thousand ten patients included: 386 (38%) died, 618 (61%) alive at discharge and six (0.6%) remained hospitalised. There was predominance of men (63%) and high frequency of overweight-obesity (71%); hypertension (54%); diabetes (40%); and lung (9%), cardiovascular (8%) and kidney diseases (11%); all of them significantly more frequent in non-survivors. Overweight-obesity was not different between groups, but severity of disease (Manchester Triage System and quick Sequential Organ Failure Assessment) was significantly worse in non-survivors, who were also significantly older (65 vs 45 years, respectively) and had haematological, biochemical, coagulation and inflammatory biomarkers more altered than survivors. Mortality predictors were invasive mechanical ventilation (IMV; OR 3.31, p