Background We aimed to examine whether acute pericarditis is an indicator of undetected cancer and identify patient-level factors associated with high cancer risk among patients presenting with pericarditis. Methods and Results A population-based matched cohort study was conducted using primary care data from the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics. Patients with acute pericarditis (n=6530) were matched to a comparison cohort (n=26 111) on age, sex, calendar time, and general practice. We estimated cumulative cancer incidences, and calculated hazard ratios using Cox regression. Effect modification by patients' characteristics and lifestyle factors was examined, and we fitted a parsimonious model to evaluate absolute excess risk of later cancer among pericarditis patients by key patient-level factors. We identified 728 and 1379 incidents of cancer among pericarditis patients and the comparison cohort (median follow-up, 2.8 and 3.5 years). Pericarditis was associated with an elevated subsequent risk of any cancer (hazard ratio=3.03; 95% confidence interval, 2.74-3.36). The association was particularly pronounced 0 to 3 months after pericarditis (hazard ratio=23.56; 95% confidence interval, 18.00-30.83), but a more-modest association remained thereafter (hazard ratio=1.95; 95% confidence interval, 1.48-2.57 after 3-12 months, and hazard ratio=1.40; 95% confidence interval, 1.21-1.62 after >12 month). Older individuals hospitalized with pericarditis and with combinations of obesity and smoking were at the highest excess risk of having a cancer diagnosis 3 to 12 months later, reaching 4.8%. Conclusions Occult cancers may be going undiagnosed during the acute episode of pericarditis. Patients presenting with pericarditis and combinations of older age, obesity, smoking, and a need for hospitalization might warrant targeted investigations for cancer.