In countries with concentrated HIV epidemics, optimizing screening to reach individuals with undiagnosed infection is essential. The DICI-VIH study, a cluster-randomized crossover trial conducted in eight French emergency departments (EDs), found that a strategy combining nurse-driven targeted HIV screening with routine diagnostic testing was effective. The aim was to investigate factors associated with the implementation of HIV screening targeting key populations in EDs. A self-administered questionnaire was distributed at registration to patients aged 18-64 years and able to give consent during the DICI-VIH intervention. Based on their responses, those belonging to key populations were offered a rapid test by triage nurses. Two key stages of the process were evaluated: questionnaire distribution by providers and test acceptance by patients. Patient information, daily workload, and ED characteristics were collected. The associations between these variables and (a) the proportion of questionnaires distributed and (b) the proportion of tests accepted were evaluated using multilevel modeling in order to examine differences in screening implementation between EDs. Questionnaire distribution proportions varied from 23% to 48% across EDs. They were higher on weekdays than weekends (odds ratio, OR: 3.77; 95% CI: 3.57-3.99) and when research staff participated (OR: 1.31; 95% CI: 1.26-1.37). They decreased over time (OR: 0.76; 95% CI: 0.71-0.82; 4th [Q3] vs. 1st quartile [Q0] of intervention days) and with increased patient flow (OR: 0.61; 95% CI: 0.56-0.67; Q3 vs. Q0 of eligible patients). Test acceptance varied from 64% to 77% across EDs, increased with research staff participation (OR 1.20; 95% CI: 1.03-1.40), and decreased over time (OR: 0.75; 95% CI: 0.60-0.92; Q3 vs. Q0). Patients who accepted were more likely to be younger (OR: 0.76; 95% CI: 0.61-0.96; 50-64-year-old vs. 30-39-year-old patients). Patient flow, intervention duration, weekdays, and research staff participation were important determinants of targeted screening implementation. These findings could help guide future implementation in similar settings. © 2019 Sigma Theta Tau International.