Atmospheric particulate matter (PM) has multiple adverse effects on human health, high temperatures are also associated with adverse health outcomes, and the frequency of cardiovascular events (CVEs) varies with season. We investigated a hypothesized increase in PM-related accident and emergency (A&E) presentations for CVE with high temperature, warm season, days of high influenza incidence, and in people with a cancer diagnosis, using a time-stratified case-crossover study design. Outcomes were associations of A&E presentation for CVE with atmospheric PM ≤ 10 μm (PM10), season, and air temperature. PM10 levels in the municipality of residence (exposure variable) were estimated by modeling data from local monitoring stations. Conditional logistic regression models estimated odds ratios (OR) with 95% confidence intervals (CI) for presentations in relation to supposed influencers, adjusting for confounders. Study participants were all who presented at the A&E of a large hospital near Milan, Italy, for a CVE (ICD-9: 390–459) from 1st January 2014 to 31st December 2015. There were 1349 A&E presentations for CVE in 2014–2015 and 5390 control days. Risk of A&E presentation was significantly increased on hot days with OR 1.34 (95%CI 1.05–1.71) per 10 μg/m3 PM10 increment (as mean PM10 on day of presentation, and 1 and 2 days before (lags 0–2)), and (for lag 0) in autumn (OR 1.23, 95%CI 1.09–1.37) and winter (OR 1.18, 95%CI 1.01–1.38). Risks were also significantly increased when PM10 was on lag 1, in people with a cancer diagnosis in the spring and summer months (1.88, 95%CI 1.05–3.37), and on days (lags 0–2) of high influenza incidence (OR 2.34, 95%CI 1.01–5.43). PM10 levels exceeded the 50 μg/m3 “safe” threshold recommended by the WHO and Italian legislation for only 3.8% of days during the warm periods of 2014–2015. Greater risk of A&E presentation for CVE in periods of high PM10 and high temperature suggests that “safe” thresholds for PM10 should be temperature-dependent and that the adverse effects of PM10 will increase as temperatures increase due to climate change.