[4] Around early 2020, Ladapo began to write op-eds for The Wall Street Journal on the emerging COVID-19 pandemic, notwithstanding a lack of specialization in infectious diseases, and gained prominence as a skeptic of mainstream consensus on prevention and treatment.

[4] In these columns, Ladapo promoted unproven treatments, including hydroxychloroquine and ivermectin, questioned the safety of vaccines, and opposed lockdown and mask mandates deriving from his "experience in treating COVID-19 patients at University of California, Los Angeles.

[18][19] Later that year, Ladapo signed the Great Barrington Declaration, which argued for reaching COVID-19 herd immunity by the fringe notion of "focused protection", where the less vulnerable people were allowed to be infected.

[34] Across 2022, Ladapo has also focused on opposing transgender health care, accusing professional organizations such as the American Academy of Pediatrics and the Endocrine Society of being politically motivated to support such causes.

He opposes gender-affirming care and counseling, hormonal therapies, related medications for transgender and nonbinary children and teenagers, and social-transition tools such as pronoun and name changes.

"[35][36] Ladapo's advice contradicts CDC guidance, which suggests that anyone not previously infected with measles or immunized against the disease observe a 21-day quarantine.

[37] Katelyn Jetelina and Kristen Panthagani, writing for Scientific American, referred to Ladapo's advice that children without immunization to measles could continue attending school after exposure as "unprecedented and dangerous".

[38] Leana Wen, in a column published by the Washington Post, characterized Ladapo's decision as "outrageous" due to the danger posed by measles.