Introduction: There have been no time-series studies of air pollution in Peru. Here we evaluate the effect of ambient PM2.5 on emergency room (ER) visits in Lima. Methods: We estimated daily PM2.5 levels at a 1 km2 resolution during 2010–2016 using ground measurements, satellite data, and chemical transport model simulations. Population-weighted average daily PM2.5 levels were calculated for each district in Lima (n = 40), and assigned to patients based on residence. ER visits for respiratory and circulatory diseases were gathered from nine large public hospitals. Poisson regression was used to estimate the rate ratio for daily ER visits with change in daily PM2.5, controlling for meteorology, time trends, and district. Results: For each interquartile range (IQR) increase in PM2.5, respiratory disease ER visits increased 4% (95% CI: 0–5%), stroke visits 10% (3–18%), and ischemic heart disease visits (adults, 18–64 years) 11% (−1, 24%). Districts with higher poverty showed significantly stronger associations of PM2.5 and respiratory disease ER visits than districts with lower poverty. Effects were diminished 24–42% using Lima-wide instead of district-specific PM2.5 levels. Conclusions: Short-term exposure to ambient PM2.5 is associated with increases in ER visits in Lima for respiratory diseases and stroke, and among middle-aged adults, ischemic heart disease.