Background: We aimed to describe changes in characteristics and treatment strategies of hospitalised patients with COVID-19 and detail the mortality trend over time. Methods: Observational cohort study of all consecutive patients admitted ≥ 48 h to Hospital Clinic of Barcelona for COVID-19 (1 March–30 September 2020). Findings: A total of 1645 consecutive patients with COVID-19 were assessed over a 7-month period. Overall mortality (≤30 days) was 9.7% (159 patients), 7.7% in patients hospitalised in regular wards and 16.7 % in patients requiring ICU admission. Overall mortality decreased from 11.6% in the first month to 1.4% in the last month, reflecting a progressive, significant downward trend (p for trend <0.001). Patients’ age changed over time, peaking in June. Most changes in the use of antivirals and anti-inflammatory treatments were documented. Age (OR 1.1, CI 1.1–1.12), chronic heart disease, (OR 1.7, CI 1.1–2.9), D-dimer>700 ng/mL (OR 2.3, CI 1.3–4.1), ferritin>489 ng/mL (OR 1.9; CI 1.5–3.2), C-RP>7 mg/dL (OR 2.6; CI 1.5–4.6), and shorter duration from symptom onset to hospital admission (OR 1.11; CI 1.04–1.17) were factors associated with 30-day mortality at hospital admission. Conversely, hospital admission in the last months (OR 0.80; CI 0.65–0.98) was significantly associated with lower mortality. Interpretation: In-hospital mortality has decreased in patients with COVID-19 over the last, few months, even though main patient characteristics remain similar. Several changes made when managing patients may explain this decreasing trend. Our study provides current data on mortality of patients hospitalised with COVID-19 that might be useful in establishing quality of standard of care. Funding: EIT Health, European Union´s Horizon 2020 Research and Innovation Programme), EDRD. PPA [CM18/00132], NGP [FI19/00133], and CGV [FIS PI18/01061], have received grants from Ministerio de Sanidad y Consumo, ISCIII.