Background The application of test-negative design case-control studies to assess the effectiveness of influenza vaccine has increased substantially in the past few years. The validity of these studies is predicated on the assumption that confounding bias by risk factors is limited by design. We aimed to assess the effectiveness of influenza vaccine in a high-risk group of elderly people. Methods We searched the Cochrane library, Medline, and Embase up to July 13, 2014, for test-negative design case-control studies that assessed the effectiveness of seasonal influenza vaccine against laboratory confirmed influenza in community-dwelling people aged 60 years or older. We used generalised linear mixed models, adapted for test-negative design case-control studies, to estimate vaccine effectiveness according to vaccine match and epidemic conditions. Findings 35 test-negative design case-control studies with 53 datasets met inclusion criteria. Seasonal influenza vaccine was not significantly effective during local virus activity, irrespective of vaccine match or mismatch to the circulating viruses. Vaccination was significantly effective against laboratory confirmed influenza during sporadic activity (odds ratio [OR] 0·69, 95% CI 0·48–0·99) only when the vaccine matched. Additionally, vaccination was significantly effective during regional (match: OR 0·42, 95% CI 0·30–0·60; mismatch: OR 0·57, 95% CI 0·41–0·79) and widespread (match: 0·54, 0·46–0·62; mismatch: OR 0·72, 95% CI 0·60–0·85) outbreaks. Interpretation Our findings show that in elderly people, irrespective of vaccine match, seasonal influenza vaccination is effective against laboratory confirmed influenza during epidemic seasons. Efforts should be renewed worldwide to further increase uptake of the influenza vaccine in the elderly population. Funding None.