Background: Short-term exposure to NO2 has been associated with adverse health effects and there is increasing concern that NO2 is causally related to health effects, not merely a marker of traffic-generated pollution. No comprehensive meta-analysis of the time-series evidence on NO2 has been published since 2007. Objective: To quantitatively assess the evidence from epidemiological time-series studies published worldwide to determine whether and to what extent short-term exposure to NO2 is associated with increased numbers of daily deaths and hospital admissions. Design: We conducted a quantitative systematic review of 204 time-series studies of NO2 and daily mortality and hospital admissions for several diagnoses and ages, which were indexed in three bibliographic databases up to May 2011. We calculated random-effects estimates by different geographic regions and globally, and also tested for heterogeneity and small study bias. Results: Sufficient estimates for meta-analysis were available for 43 cause-specific and age-specific combinations of mortality or hospital admissions (25 for 24 h NO2 and 18 of the same combinations for 1 h measures). For the all-age group, a 10 µg/m3 increase in 24 h NO2 was associated with increases in all-cause, cardiovascular and respiratory mortality (0.71% (95% CI 0.43% to 1.00%), 0.88% (0.63% to 1.13%) and 1.09% (0.75% to 1.42%), respectively), and with hospital admissions for respiratory (0.57% (0.33% to 0.82%)) and cardiovascular (0.66% (0.32% to 1.01%)) diseases. Evidence of heterogeneity between geographical region-specific estimates was identified in more than half of the combinations analysed. Conclusions: Our review provides clear evidence of health effects associated with short-term exposure to NO2 although further work is required to understand reasons for the regional heterogeneity observed. The growing literature, incorporating large multi-centre studies and new evidence from less well-studied regions of the world, supports further quantitative review to assess the independence of NO2 health effects from other air pollutants.