Evidence on health effects of ultrafine particles (UFP) is still limited as they are usually not monitored routinely. The few epidemiological studies on UFP and (cause-specific) mortality so far have reported inconsistent results. The main objective of the UFIREG project was to investigate the short-term associations between UFP and fine particulate matter (PM)<2.5μm (PM2.5) and daily (cause-specific) mortality in five European Cities. We also examined the effects of PM<10μm (PM10) and coarse particles (PM2.5–10). UFP (20–100nm), PM and meteorological data were measured in Dresden and Augsburg (Germany), Prague (Czech Republic), Ljubljana (Slovenia) and Chernivtsi (Ukraine). Daily counts of natural and cardio-respiratory mortality were collected for all five cities. Depending on data availability, the following study periods were chosen: Augsburg and Dresden 2011–2012, Ljubljana and Prague 2012–2013, Chernivtsi 2013–March 2014. The associations between air pollutants and health outcomes were assessed using confounder-adjusted Poisson regression models examining single (lag 0–lag 5) and cumulative lags (lag 0–1, lag 2–5, and lag 0–5). City-specific estimates were pooled using meta-analyses methods. Results indicated a delayed and prolonged association between UFP and respiratory mortality (9.9% 95%-confidence interval: −6.3%; 28.8% increase in association with a 6-day average increase of 2750particles/cm3 (average interquartile range across all cities)). Cardiovascular mortality increased by 3.0% −2.7%; 9.1% and 4.1% 0.4%; 8.0% in association with a 12.4μg/m3 and 4.7μg/m3 increase in the PM2.5- and PM2.5–10-averages of lag 2–5. We observed positive but not statistically significant associations between prolonged exposures to UFP and respiratory mortality, which were independent of particle mass exposures. Further multi-centre studies are needed investigating several years to produce more precise estimates on health effects of UFP. •We investigated the associations between ultrafine and fine particles and (cause-specific) mortality in multiple locations.•The UFIREG study included cities from Central and Eastern European countries.•Results indicated a delayed and prolonged association between ultrafine particles and respiratory mortality.•PM2.5 and PM2.5–10 were associated with delayed increases in cardiovascular mortality.