Introduction: Understanding the pandemic characteristics and risk factors associated with COVID-19 infection among healthcare workers (HCWs) in hospitals is crucial for both preventing and controlling the spread of COVID-19 and safeguarding healthcare personnel. In our study, our objective was to examine the risk factors for SARS-CoV-2 infection among HCWs and to assess the disease's transmission characteristics and impact on the workforce. Materials and Methods: Healthcare workers at Ankara Bilkent Sehir Hastanesi with positive (cases) and negative (control) results on SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) tests were enrolled. Following the initial case in our country, follow-up forms were implemented for HCWs with a history of contact and COVID-19 infection at our hospital. Healthcare workers were subjected to active surveillance for follow-up. Demographic characteristics of HCWs, including occupation, the unit of employment, and risky contact status, were documented. Additionally, the duration of hospitalization for cases, administered treatments, and overall workforce loss were assessed. A comparison between the case and control groups was conducted regarding the aforementioned characteristics to explore factors influencing the onset of COVID-19 infection among HCWs. The SPSS 18.0 software was utilized for data analysis. Results: One thousand five hundred fifty-nine cases were evaluated. The mean age of the patients was 31.3 +/- 8.61, and 75.1% were male. At the time of diagnosis, 50.9% of the HCWs were assigned to non-COVID-19 areas, 24.6% were working in the COVID-19 intensive care unit (ICU), and 24.5% were stationed in the COVID-19 ward. Fifty-one point three percent of the cases had a risky contact history. Risky contact was most frequently reported with patients (43.2%) and via close contact (99.3%). Of the cases, 84.2% exhibited symptoms, and 141 individuals were monitored through hospitalization. The hospitalization duration was 10.1 +/- 13.9 days (1-150 days). The total workforce loss was 12.9 +/- 7.1 days (median 10 days). Recovery was observed in 99.9% of cases. In a multivariate analysis of 742 individuals in the control group and 1559 in the case group, it was found that compared to individuals working in non-COVID-19 areas, those working in COVID-19 wards experienced a 70.2% lower risk of SARS-CoV-2 RT-PCR positivity. Similarly, those working in COVID-19 ICUs had a 57.8% lower risk (OR= 0.298, 95% CI= 0.225-0.394, p< 0.001, OR= 0.422, 95% CI= 0.308-0.577; p< 0.001, respectively). Conclusion: During a pandemic, all healthcare workers need to exercise caution regardless of their work setting, not just those in high -risk areas.