Background: Hereditary angioedema with C1 inhibitor deficiency (HAE-C1INH) is a rare disease characterized by swelling episodes. It affects quality of life (QoL) and can be lethal, when involving upper airways. Treatment is individualized, with therapeutic options including on-demand treatment (ODT), and short- and long-term prophylaxis (STP, LTP). However, available guidelines are not always clear about treatment selection, its goals or assessment of goal achievement. Objective: To review the available evidence for the management of HAE-C1INH and build a Spanish expert consensus to steer HAE-C1INH management towards a treat-to-target (T2T) approach, while addressing some of the unclear aspects of the Spanish guidelines. Methods: We reviewed the literature on the management of HAE-C1INH with a T2T approach, focusing on: 1) treatment selection and goals; and 2) available tools to assess goal achievement. We discussed the literature based on clinical experience and drew up 45 statements on undefined management aspects. A panel of 53 HAE experts validated the statements through a two-round Delphi process. Results: The goals for ODT and STP are minimizing the morbidity and mortality of attacks, and preventing attacks caused by known triggers, respectively, while the main goal of LTP is to decrease the rate, severity and duration of attacks. Furthermore, when prescribing, clinicians should consider the reduction in adverse events, while increasing patient QoL and satisfaction. Appropriate instruments for assessing goal achievement have also been indicated. Conclusions: We provide recommendations on previously unclear aspects of HAE-C1INH management with ODT, STP and LTP, focusing particularly on clinical and patient-oriented goals.