AbstractObjective:To determine risk factors for the development of long coronavirus disease 2019 (COVID-19) in healthcare personnel (HCP).Methods:We conducted a case–control study among HCP who had confirmed symptomatic COVID-19 working in a Brazilian healthcare system between March 1, 2020, and July 15, 2022. Cases were defined as those having long COVID according to the Centers for Disease Control and Prevention definition. Controls were defined as HCP who had documented COVID-19 but did not develop long COVID. Multiple logistic regression was used to assess the association between exposure variables and long COVID during 180 days of follow-up.Results:Of 7,051 HCP diagnosed with COVID-19, 1,933 (27.4%) who developed long COVID were compared to 5,118 (72.6%) who did not. The majority of those with long COVID (51.8%) had 3 or more symptoms. Factors associated with the development of long COVID were female sex (OR, 1.21; 95% CI, 1.05–1.39), age (OR, 1.01; 95% CI, 1.00–1.02), and 2 or more SARS-CoV-2 infections (OR, 1.27; 95% CI, 1.07–1.50). Those infected with the SARS-CoV-2 δ (delta) variant (OR, 0.30; 95% CI, 0.17–0.50) or the SARS-CoV-2 o (omicron) variant (OR, 0.49; 95% CI, 0.30–0.78), and those receiving 4 COVID-19 vaccine doses prior to infection (OR, 0.05; 95% CI, 0.01–0.19) were significantly less likely to develop long COVID.Conclusions:Long COVID can be prevalent among HCP. Acquiring >1 SARS-CoV-2 infection was a major risk factor for long COVID, while maintenance of immunity via vaccination was highly protective.