BACKGROUND: Hyperkalemia is a common condition in patients with comorbidities such as chronic kidney disease (CKD) or congestive heart failure. Moreover, severe hyperkalemia is a potentially life-threatening condition that is associated with a higher risk of adverse clinical events such as ventricular arrhythmias and sudden cardiac death. Currently, data regarding the prognostic implications of chronic hyperkalemia are available; however, the information about the long-term clinical consequences after an episode of severe hyperkalemia remains scarce. The objective of the study was to evaluate the association between the trajectory of potassium measurements in patients with acute hyperkalemia and long-term all-cause mortality. METHODS: This is a retrospective observational study that included patients with acute severe hyperkalemia (K>6 mEq/L) without hemolysis in the emergency room of Dr. Peset University Hospital in Valencia, Spain searching the lab database from January 2016 to March 2017. The multivariable-adjusted association of serum potassium with mortality was assessed by using comprehensive state-of-the-art regression methods that can accommodate time-dependent exposure modelling. RESULTS: We found 172 episodes of acute hyperkalemia in 160 patients in the emergency room. The mean age of the sample was 77±12years and 60.5% were males. The most frequent comorbidities were CKD (71.2%), heart failure (35%) and diabetes mellitus (56.9%). Only 11.9% of the patients were on chronic dialysis. A quarter of the patients did not have previous CKD making hyperkalemia as an unpredictable life-threatening complication. During the acute episode, mean potassium and eGFR were 6.6±0.6 (range: 6,1-9,2), and eGFR: 23±16 (r : 2-84). After a median follow-up of 17.3 (IQR: 2.2-23.7) months, 68 patients died (42.5%). Recurrences of hyperkalemia (K>5.5 mEq/L) were detected in 39.5%% of the patients who were monitored during follow-up. We found that previous potassium levels during an acute severe hyperkalemia episode were not predictors of mortality. Conversely, the post-discharge longitudinal trajectories of potassium were able to predict all-cause mortality (overall p-value=0.0015). The effect of transitioning from hyperkalemia to normokalaemia (K>5.5 to K=5.5 after the acute episode was significant and inversely associated with the risk of mortality. CONCLUSION: The potassium levels prior to a severe hyperkalemic event do not predict mortality. Conversely, following an episode of acute severe hyperkalemia, serial kinetic of potassium trajectories predicts the risk of death. Further evidence is needed to confirm these findings and clarify the optimal long-term management of these patients.