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Introduction: HIV treatment currently consists of daily oral antiretroviral therapy (ART). Cabotegravir + rilpivirine long-acting (CAB + RPV LA) is the first ART available in Spain administered every 2 months through intramuscular injection by a healthcare professional (HCP). The objective of this analysis was to assess potential healthcare resource use (HRU) and cost impact of implementing CAB + RPV LA vs. daily oral ART at National Health System (NHS) hospitals. Methods: Online quantitative interviews and cost analysis were performed. Infectious disease specialists (IDS), hospital pharmacists (HP) and nurses were asked about their perception of potential differences in HRU between CAB + RPV LA vs. daily oral ART, among other concepts of interest. Spanish official tariffs were applied as unit costs to the HRU estimates (€2022). Results: 120 responders (n = 40 IDS, n = 40 HP, n = 40 nurses) estimated an average number of annual visits per patient by speciality (IDS, HP, and nurse, respectively) of 3.3 vs. 3.7; 4.4 vs. 6.2; 6.1 vs. 3.9, for CAB + RPV LA vs. daily oral ART, and 3.0 vs. 3.2; 4.8 vs. 5.8; 6.9 vs. 4.9, respectively when adjusting by corresponding specialist responses. Estimation by the total sample led to an annual total cost per patient of €2,076 vs. €2,473, being €2,032 vs. €2,237 after adjusting by corresponding HCP, for CAB + RPV LA vs. daily oral ART. Conclusions: These results suggest that the implementation of CAB + RPV LA in NHS hospitals would not incur in increased HRU-related costs compared to current daily oral ARTs, being potentially neutral or even cost-saving. Why carry out this study? • Main clinical guidelines in HIV recommend the use of daily oral antiretroviral combinations. Recently, a long-acting regimen consisting of cabotegravir plus rilpivirine (CAB + RPV LA) gluteal intramuscular injections has become available in Spain for maintaining HIV-1 suppression. • Given that the long-acting regimes are administered every 2 months, it is anticipated to have a different patient pathway within the hospital compared to daily oral ART, which may lead to changes in healthcare resources and associated costs needed for HIV treatment. What was learned from the study? • The total annual cost per patient ranged from €2,032 to €2,076 for CAB + RPV LA, and from €2,237 to €2,473 for daily oral ART. • These figures suggest that the implementation of CAB + RPV LA in Spanish NHS hospitals would not translate into increased healthcare resource utilization-related costs associated to a different patient pathway compared to current daily oral ART, being potentially cost-saving. [ABSTRACT FROM AUTHOR]