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Little is known about the short-term effects of ultrafine particles.We evaluated the effect of particulate matter with an aerodynamic diameter ≤10 μm (PM10), ≤2.5 μm (PM2.5), and ultrafine particles on emergency hospital admissions in Rome 2001–2005. We studied residents aged ≥35 years hospitalized for acute coronary syndrome, heart failure, lower respiratory tract infections, and chronic obstructive pulmonary disease (COPD). Information was available for factors indicating vulnerability, such as age and previous admissions for COPD. Particulate matter data were collected daily at one central fixed monitor. A case-crossover analysis was performed using a time-stratified approach. We estimated percent increases in risk per 14 μg/m3 PM10, per 10 μg/m3 PM2.5, and per 9392 particles/mL.An immediate impact (lag 0) of PM2.5 on hospitalizations for acute coronary syndrome (2.3% [95% confidence interval = 0.5% to 4.2%]) and heart failure (2.4% [0.3% to 4.5%]) was found, whereas the effect on lower respiratory tract infections (2.8% [0.5% to 5.2%]) was delayed (lag 2). Particle number concentration showed an association only with admissions for heart failure (lag 0–5; 2.4% [0.2% to 4.7%]) and COPD (lag 0; 1.6% [0.0% to 3.2%]). The effects were generally stronger in the elderly and during winter. There was no clear effect modification with previous COPD.We found sizeable acute health effects of fine and ultrafine particles. Although differential reliability in exposure assessment, in particular of ultrafine particles, precludes a firm conclusion, the study indicates that particulate matter of different sizes tends to have diverse outcomes, with dissimilar latency between exposure and health response.