SummaryObjectiveMost epileptic seizures occur unexpectedly and independently of known risk factors. We aimed to evaluate the clinical significance of patients’ perception that weather is a risk factor for epileptic seizures.MethodsUsing a hospital‐based, bidirectional case‐crossover study, 604 adult patients admitted to a large university hospital in Central Germany for an unprovoked epileptic seizure between 2003 and 2010 were recruited. The effect of atmospheric pressure, relative air humidity, and ambient temperature on the onset of epileptic seizures under temperate climate conditions was estimated.ResultsWe found a close‐to‐linear negative correlation between atmospheric pressure and seizure risk. For every 10.7 hPa lower atmospheric pressure, seizure risk increased in the entire study population by 14% (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.01–1.28). In patients with less severe epilepsy treated with one antiepileptic medication, seizure risk increased by 36% (1.36, 1.09–1.67). A high relative air humidity of >80% increased seizure risk in the entire study population by up to 48% (OR 1.48, 95% CI 1.11–1.96) 3 days after exposure in a J‐shaped association. High ambient temperatures of >20°C decreased seizure risk by 46% in the overall study population (OR 0.54, 95% CI 0.32–0.90) and in subgroups, with the greatest effects observed in male patients (OR 0.33, 95% CI 0.14–0.74).SignificanceLow atmospheric pressure and high relative air humidity are associated with an increased risk for epileptic seizures, whereas high ambient temperatures seem to decrease seizure risk. Weather‐dependent seizure risk may be accentuated in patients with less severe epilepsy. Our results require further replication across different climate regions and cohorts before reliable clinical recommendations can be made.