Frailty and multimorbidity frequently coexist in older adults, yet their independent and combined prognostic implications in hospitalised patients remain incompletely understood. This study aimed to investigate their prognostic contribution to six-month mortality across different operationalisations of multimorbidity and levels of frailty severity.

This observational study used prospectively collected data from adults aged ≥65 years admitted to an Acute Geriatric Unit. Frailty was assessed with the Clinical Frailty Scale (CFS), while multimorbidity was operationalised as ≥2 co-existing long-term conditions (2+LTCs), and further evaluated using the Charlson Comorbidity Index (CCI) and single disease count (SC). The primary outcome was six-month mortality. Adjusted Cox models assessed independent associations of frailty and multimorbidity with mortality, as well as their interactions.

Among 2,006 patients (mean age 85.6 years; 53% female), both 2+LTCs and at least moderate frailty (CFS ≥6) were highly prevalent, each affecting 70% of participants. Overall, 445 patients (22%) died within six months after discharge. Frailty was associated with increased mortality both in the presence and absence of 2+LTCs. Across secondary models, each 1-point increase in CFS was associated with 50% higher mortality risk (all P < 0.001). 2+LTCs and CCI retained independent associations with mortality, whereas SC did not. A significant negative interaction was observed between frailty and CCI (P for interaction = 0.011), indicating attenuation of the prognostic contribution of weighted disease burden at higher frailty levels.

Frailty showed the strongest association with six-month mortality, whereas the prognostic significance of multimorbidity varied according to its operationalisation and frailty severity. These findings support broader integration of frailty assessment into prognostic stratification in hospitalised older adults.