BACKGROUND: Evidence on the association between short-term exposure to desert dust and health outcomes is controversial. OBJECTIVES: We aimed to estimate the short-term effects of particulate matter ≤ 10 μm (PM10) on mortality and hospital admissions in 13 Southern European cities, distinguishing between PM10 originating from the desert and from other sources. METHODS: We identified desert dust advection days in multiple Mediterranean areas for 2001–2010 by combining modeling tools, back-trajectories, and satellite data. For each advection day, we estimated PM10 concentrations originating from desert, and computed PM10 from other sources by difference. We fitted city-specific Poisson regression models to estimate the association between PM from different sources (desert and non-desert) and daily mortality and emergency hospitalizations. Finally, we pooled city-specific results in a random-effects meta-analysis. RESULTS: On average, 15% of days were affected by desert dust at ground level (desert PM10 > 0 μg/m3). Most episodes occurred in spring–summer, with increasing gradient of both frequency and intensity north–south and west–east of the Mediterranean basin. We found significant associations of both PM10 concentrations with mortality. Increases of 10 μg/m3 in non-desert and desert PM10 (lag 0–1 days) were associated with increases in natural mortality of 0.55% (95% CI: 0.24, 0.87%) and 0.65% (95% CI: 0.24, 1.06%), respectively. Similar associations were estimated for cardio-respiratory mortality and hospital admissions. CONCLUSIONS: PM10 originating from the desert was positively associated with mortality and hospitalizations in Southern Europe. Policy measures should aim at reducing population exposure to anthropogenic airborne particles even in areas with large contribution from desert dust advections. CITATION: Stafoggia M, Zauli-Sajani S, Pey J, Samoli E, Alessandrini E, Basagaña X, Cernigliaro A, Chiusolo M, Demaria M, Díaz J, Faustini A, Katsouyanni K, Kelessis AG, Linares C, Marchesi S, Medina S, Pandolfi P, Pérez N, Querol X, Randi G, Ranzi A, Tobias A, Forastiere F, MED-PARTICLES Study Group. 2016. Desert dust outbreaks in Southern Europe: contribution to daily PM10 concentrations and short-term associations with mortality and hospital admissions. Environ Health Perspect 124:413–419; http://dx.doi.org/10.1289/ehp.1409164