Introduction: The best-established cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease are levels of amyloid β 42 (Aβ42), total tau (tau), and phosphorylated tau 181 (ptau). We examined whether a widely used commercial immunoassay for CSF Aβ42, tau, and ptau provided stable measurements for more than ∼10 years. Methods: INNOTEST assay values for CSF Aβ42, tau, and ptau from Washington University in St. Louis and VU Medical Center, Amsterdam, were evaluated. Results: Aβ42 values as measured by the INNOTEST assay drifted upward by approximately 3% per year over the past decade. Tau values remained relatively stable, whereas results for ptau were mixed. Discussion: Assay drift may reduce statistical power or even confound analyses. The drift in INNOTEST Aβ42 values may reduce diagnostic accuracy for Alzheimer's disease in the clinic. We recommend methods to account for assay drift in existing data sets and to reduce assay drift in future studies.