Why was variolation less safe than vaccination with cowpox?

Variolation was less safe than vaccination with cowpox because it involved intentionally infecting individuals with the actual smallpox virus, typically taken from the sores of someone with a mild case. Because the procedure used the live smallpox virus, recipients could develop full-blown, dangerous cases of the disease and potentially spread it to others.1

In contrast, Edward Jenner discovered that cowpox—a much milder virus—provided immunity against smallpox because the two viruses share common antigens. Vaccination with cowpox allowed the immune system to develop protection without the significant risk of the patient contracting the deadly smallpox disease itself. Consequently, vaccination became the safer, preferred method for immunization, eventually leading to the global eradication of smallpox.12