Healthcare-associated infections (HAIs) represent a significant challenge in hospital settings, contributing to increased morbidity, mortality, and healthcare costs. This study aimed to estimate the prevalence and socio-demographic and clinical determinants of HAIs at the King Abdulaziz Specialized Hospital (KAASH) in Taif, Saudi Arabia. A hospital-based cross-sectional study was conducted from March 2023 to January 2024targeting inpatients aged 18 and above in all units and wards. Data were collected using the National Healthcare Safety Network (NHSN) criteria for definitions of surveillance. A structured questionnaire gathered socio-demographic and clinical data from patients or next of kin if the patient was not fully oriented.Descriptive statistics were performed, and analytical methods used included Pearson chi-square test, Pearsoncorrelation, independent t-test, and one-way analysis of variance. Among 318 participants included in this study, the mean age of participants was 56.44 years, with a slight female predominance (n=164, 51.6%). Hypertension (n=162, 50.9%) and diabetes (n=126, 39.6%) were the most prevalent comorbidities. Pneumonia (n=60, 26.8%) and trauma (n=55, 17.4%) were the leading causes of admission. The two most common HAIs included catheter-associated urinary tract infections (CAUTI) (n=124, 39%) and central line-associated bloodstream infections (CLABSI) (n=74, 23.3%). The primary causative organisms were Klebsiella pneumoniae (n=96, 30.2%) and Acinetobacter baumannii (n=32, 10.1%). The most significant predictors of HAIs were as follows: For CLABSI, risk factors include having three or more comorbidities, fever above 37.8°C, chills or rigors, hypotension, and positive blood culture. For CAUTI, key predictors were urinary tract infection (UTI), positive urine culture, acute pain or swelling of the testes, suprapubic tenderness, visible hematuria, and leukocytosis. Significant predictors of bloodstream infections (BSI) include having a BSI, positive blood culture, chills or rigors, and hypotension. Fever and hypotension increased CLABSI and BSI risk but reduced the CAUTI risk. The study highlights a significant burden of HAIs at the KAASH, with multiple predictors. The findings underscore the need for robust infection control measures and targeted interventions to reduce HAI incidence and improve patient outcomes.