ABSTRACT Objectives: A number of studies have compared Alzheimer’s disease (AD), the commonest form of dementia, based on their age of onset, i.e. before the age of 65 years (early-onset AD, EO-AD) to those developing after 65 years of age (late-onset AD, LO-AD), but the differences are not clear. We performed a systematic review and meta-analysis to compare clinical characteristics between EO-AD and LO-AD. Design, measurements, and participants: Medline, Embase, PsycINFO, and CINAHL databases were systematically searched for studies comparing time to diagnosis, cognitive scores, annual cognitive decline, activities of daily living (ADLs), neuropsychiatric symptoms (NPS), quality of life (QoL), and survival time for EO-AD and LO-AD patients. Results: Forty-two studies were included (EO-AD participants n = 5,544; LO-AD participants n = 16,042). An inverse variance method with random effects models was used to calculate overall effect estimates for each outcome. People with EO-AD had significantly poorer baseline cognitive performance and faster cognitive decline but longer survival times than people with LO-AD. There was no evidence that EO-AD patients differ from people with LO-AD in terms of symptom onset to diagnosis time, ADLs, and NPS. There were insufficient data to estimate overall effects of differences in QoL in EO-AD compared to LO-AD. Conclusions: Our findings suggest that EO-AD differs from LO-AD in baseline cognition, cognitive decline, and survival time but otherwise has similar clinical characteristics to LO-AD. Larger studies using standardized questionnaires focusing on the clinical presentations are needed to better understand the impact of age of onset in AD.