Potassium levels (K, mEq/L) fluctuate in patients with acute myocardial infarction (AMI). Potassium was reported to be associated with prognosis in patients with AMI; however, studies evaluating the prognostic value of K fluctuations in this setting are scarce. We retrospectively analyzed patients with AMI hospitalized in a tertiary medical center, through 2002 to 2012. Patients on chronic dialysis or mechanical ventilation were excluded. Based on all K values during hospitalization, minimal, maximal, and fluctuation (gap between 2 consecutive K) were recorded. Primary outcome was inhospital all-cause mortality. Overall, 10 032 patients were studied (age 68.1 ± 14.3 years, 65.4% males, 44.2% ST-segment elevation MI), of which 507 (3.7%) died in hospital. Potassium decreased during the first 2 to 3 days (P for trend <.001), followed by stabilization (P for trend = .807). Potassium in the extreme categories (<3.8 and ≥4.7) and absolute fluctuations >0.1 mEq/L were more common among nonsurvivors than survivors (P < .001 each). In a multivariate analysis, combinations of minimal K <3.8 with maximal K ≥4.7 (odds ratio [OR] = 18.1), K ≥4.4 with fluctuation ≥0.1 (OR = 1.74), or <−0.1 (OR = 2.6) and minimal K after the first 2 admission days (OR = 2.07) were associated with increased risk of mortality (P < .001 each). Potassium fluctuations, peak and nadir K, and its timing independently predict inhospital mortality in patients with AMI.