BackgroundHas either the underlying risk or the mortality incidence among ICU patients receiving mechanical ventilation (MV) in the literature changed in recent decades? Interpreting ICU mortality trends requires an adjusted analysis accounting for changes in underlying patient risk.MethodsControl and intervention groups from 147 randomized concurrent control trials (RCCT) of various VAP prevention interventions, as listed primarily within 13 Cochrane reviews and 63 observational studies listed﻿ primarily within four systematic reviews. Eligible studies were those including ICU patients with > 50% of patients receiving > 24 h of MV with mortality data available. ICU mortality (censored day 21 or before) or late (after day 21) mortality together with group-mean age, and group-mean APACHE II scores were extracted from all groups. These incidences were summarized in five meta-regression models versus publication year being variously adjusted for age, APACHE II scores, type of study intervention and other group level parameters.ResultsAmong 210 studies published between 1985 and 2021, 169 being found in systematic reviews, the increase per decade in mean mortality incidence, group-mean APACHE II scores, and group-mean age, were < 1 percentage point (p= 0.43), 1.83 (95% CI; 0.51–3.15) points, and 3.9 (95% CI; 1.1–6.7) years, respectively. Only in the model with risk adjustment for both group-mean age and group-mean APACHE II score was a significant decline in mortality apparent. In all models, the mortality incidence among concurrent control groups of decontamination studies was paradoxically five percentage points higher than benchmark and showed greater dispersion.ConclusionMortality incidence has changed little over 35 years among ICU infection prevention studies whilst the patient age and underlying disease severity, measured as APACHE II, have both increased. The paradoxically high mortality among concurrent control groups within studies of decontamination methods of infection prevention remains unaccounted for.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13613-023-01159-0.