This study investigates the validity of questionnaire-based self-reports of illicit drug use by comparing with a two-tiered urinalysis among patients at emergency departments. Questions on the use of alcohol and drugs were administered to patients recruited on a continual basis for 2weeks at the emergency department of two hospitals in northern Taiwan. Positive tests of initial urinalysis using fluorescence polarization immunoassay were further confirmed by gas chromatography/mass spectrometry. In a total of 1502 patients interviewed, 632 (42%) also provided a urine sample. Among those with urine samples, the positive rate of urinalysis was 1.4% for amphetamine-type drugs and 1.6% for opiates. Among those with positive urinalysis, a false-negative rate ranged from 66.6% for amphetamines to 70.0% for opiates. Meanwhile, all the self-reported current uses of either amphetamines or opiates were confirmed by urinalysis. The results indicate that the false-negative rates of questionnaire-based, self-reported current use of illicit drug are around two thirds and the false-positive rates are negligible, which might be useful for the calibration of estimates from epidemiological surveys.