While thrombocytopenia's link to mortality is known, the prognostic impact of longitudinal trajectories of platelet indices in combination with analysis of thrombocytopenia's mediating role remains unexplored. This is the first study that addresses this significant gap by investigating the association between seven platelet indices trajectory subphenotypes and ICU mortality, considering thrombocytopenia's mediating influence. Four hundred and twenty-one adult ICU patients were enrolled in this longitudinal cohort study. Three trajectories were identified for each platelet index, namely: descending, stable, and ascending, and using a regression, receiver-operating characteristic curve, and mediation analysis, their associations with 90-day mortality were evaluated with the mediating effect of thrombocytopenia. The findings were adjusted (prefixed 'a') for covariates. The heterogeneous trajectories significantly associated with 90-day mortality included: descending platelet count (PC) [aOR, 2.75 (CI, 1.56-4.85),