Purpose Changes of lactate concentration over time were reported to be associated with survival in septic patients. We aimed to evaluate delta-lactate (ΔLac) 24 h after admission (Δ24Lac) to an intensive care unit (ICU) in critically ill patients for short- and long-term prognostic relevance. Methods In total, 26,285 lactate measurements of 2191 patients admitted to a German ICU were analyzed. Inclusion criterion was a lactate concentration at admission above 2.0 mmol/L. Maximum lactate concentrations of day 1 and day 2 were used to calculate Δ24Lac. Follow-up of patients was performed retrospectively. Association of Δ24Lac and both in-hospital and long-term mortality were investigated. An optimal cut-off was calculated by means of the Youden index. Results Patients with lower Δ24Lac were of similar age, but clinically sicker. As continuous variable, higher Δ24Lac was associated with decreased in-hospital mortality (per 1% Δ24Lac; HR 0.987 95%CI 0.985–0.990; p  < 0.001) and an optimal Δ24Lac cut-off was calculated at 19%. Δ24Lac ≤ 19% was associated with both increased in-hospital (15% vs 43%; OR 4.11; 95%CI 3.23–5.21; p  < 0.001) and long-term mortality (HR 1.54 95%CI 1.28–1.87; p  < 0.001), even after correction for APACHE II, need for catecholamines and intubation. We matched 256 patients with Δ24Lac ≤ 19% to case–controls > 19% corrected for APACHE II scores, baseline lactate level and sex: Δ24Lac ≤ 19% remained associated with lower in-hospital and long-term survival. Conclusions Lower Δ24Lac was robustly associated with adverse outcome in critically ill patients, even after correction for confounders. Δ24Lac might constitute an independent, easily available and important parameter for risk stratification in the critically ill.