PURPOSE: To compare the efficacy of clindamycin versus cefazolin in preventing periprosthetic joint infection (PJI) in patients undergoing hip hemiarthroplasty (HA) for femoral neck fractures. METHODS: This retrospective cohort study included 1,139 patients aged ≥ 65 years who underwent HA for femoral neck fractures between January 2017 and October 2023. Patients received either Cefazolin + Gentamicin (n = 1001) or Clindamycin + Gentamicin (n = 138). Propensity score matching was performed at a 6:1 ratio, resulting in 828 patients in the cefazolin group and 138 in the clindamycin group. PJI rates, causative organisms, and mortality were compared. Multivariate logistic regression adjusted for potential confounders. RESULTS: The PJI rate was significantly higher in the clindamycin group compared to the cefazolin group (7.2% vs. 3.5%, p = 0.042). Multivariate analysis confirmed that clindamycin prophylaxis was independently associated with increased PJI risk (adjusted OR = 2.41, 95% CI: 1.16-4.99, p = 0.018). Other independent risk factors for PJI included age (adjusted OR = 1.03 per year, 95% CI: 1.01-1.05, p = 0.045), diabetes mellitus (adjusted OR = 1.76, 95% CI: 1.10-2.81, p = 0.018), and surgery duration (adjusted OR = 1.07 per minute, 95% CI: 1.01-1.16, p = 0.035). Staphylococcus aureus was the most common pathogen, with no significant differences in bacterial distribution between the groups. No significant differences were found in 30-day or 1-year mortality rates. CONCLUSION: Clindamycin prophylaxis in hip hemiarthroplasty for femoral neck fractures is associated with a significantly higher risk of PJI compared to cefazolin. These findings support the preferential use of cefazolin in patients without contraindications and demonstrate the critical need for accurate assessment of reported beta-lactam allergies. Results suggest potential benefit from pre-operative allergy evaluation when feasible, as alternative prophylaxis choices may carry increased infection risk. Further research is needed to explore alternative prophylactic strategies for patients with beta-lactam allergies.