Background: Alterations derived from lymphedema in the upper-limb secondary to breast cancer-related lymphedema (BCRL) decrease the health-related quality of life (HRQoL), but there is limited evidence of the impact of the different interventions on it. The aim of this research was to compare the effect of conventional treatment with another treatment based on Activity-Oriented Antiedema Proprioceptive Therapy (TAPA) on HRQoL in women diagnosed with BCRL. Methods: A prospective clinical study was designed with two parallel arms. The study population consisted of women diagnosed with BCRL in stage I and II, belonging to different institutions in Córdoba and Aragon, Spain. Sociodemographic and HRQoL-related variables, pain, tightness, heaviness and functionality were obtained before and after treatments. Results: 51 women participated in the study, 25 received the conventional treatment and 26 the TAPA, with a mean age of 59.24 ± 9.55 years. HRQoL was significantly related to upper-limb function and pain on the participants’ affected side. In addition, covariance analysis (ANCOVA) showed that the TAPA treatment interfered less in the performance of activities of daily life and produced significant improvements in the social dimension of HRQoL. Conclusions: the non-use of compressive elements in the rehabilitative treatment of the BCRL that is proposed with TAPA improves aspects such as self-image and participation in social and recreational activities.