Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Instituto de Salud Carlos III (ISCIII) (PI10/02763, PI10/02745, PI18/00449, PI19/00907), co-funded by FEDER “Una manera de hacer Europa”, SEPAR, Catalonian Cardiology Society, ResMed Ltd. (Australia), EsteveTeijin (Spain), Oxigen Salud (Spain), Associació Lleidatana de Respiratori (ALLER), CIBERES. MS received financial support from a "Ramón y Cajal" grant (RYC2019-027831-I) from the“Ministerio de Ciencia e Innovación - Agencia Estatal de Investigación” co-funded by the European Social Fund (ESF)/“Investing in your future”. AZ held the predoctoral fellowship “Ajuts 2021 de Promoció de la Recerca en Salut-9ª edició” from IRBLleida/Diputació de Lleida. JdB acknowledges receiving financial support from ISCIII (Miguel Servet 2019: CP19/00108), co-funded by the European Social Fund (ESF), “Investing in your future”. Rationale Obstructive sleep apnea (OSA) is prevalent in acute coronary syndrome (ACS) patients and is a cause of secondary hypertension. Objectives To evaluate the long-term effects of OSA and CPAP treatment on blood pressure (BP) control in patients discharged after an ACS. Methods Post hoc analysis of the ISAACC study included 1803 patients admitted for ACS (NCT01335087). Patients with OSA (apnea-hypopnea index ≥15 events/h) were randomly assigned to receive either CPAP or/and usual care and followed up for one to 5 years. Office BP was determined at each visit. Measurements and Main Results We included 596 patients without OSA, 605 patients in the CPAP group, and 602 patients in the usual care group. 52% of the patients had a diagnosis of hypertension at baseline. Median age and body mass index were 59 [52.0;67.0] years and 28.2 [25.6;31.2] kg/m2, respectively. After a median [25th;75th percentile] follow-up of 41.2 [18.3;59.6] months, BP changes were similar between OSA and non-OSA groups. However, we observed an increase in BP in the third tertile of the AHI (AHI>40 events/h) with a maximum difference in mean BP of +3.3 mmHg at 30 months. OSA patients with good CPAP adherence (≥4 hours/night) reduced mean BP after 18 months compared to non-OSA and poor CPAP adherence patients, maximum mean difference (95% CI) of -4.7 (-6.7,-2.7) mmHg. In patients with severe OSA we observed a maximum mean difference of -7.1 (-10.3,-3.8) mmHg. Conclusions In patients discharged after an ACS, severe OSA is associated with a long-term increase in BP, which is reduced by good CPAP adherence.