(1) Background: Acute respiratory distress syndrome (ARDS) following cardiac arrest is common and associated with in-hospital mortality. We aim to investigate whether lung compliance during targeted temperature management is associated with neurological outcome in patients with ARDS after out-of-hospital cardiac arrest (OHCA). (2) Methods: This observational study is conducted in the emergency intensive care unit from January 2011 to April 2019 using data from a prospective patient registry. Adult patients (age ≥18 years) who survived non-traumatic OHCA and subsequently developed ARDS based on the Berlin definition are included. Mechanical ventilator parameters such as plateau pressure, tidal volume, minute ventilation, positive end expiratory pressure, and compliance are recorded for 7 days or until death, and categorized as maximum, median, and minimum. The primary outcome is a favorable neurological outcome defined as a Cerebral Performance Category score of 1 or 2 at hospital discharge. (3) Results: Regarding 246 OHCA survivors, 119 (48.4%) patients developed ARDS. A favorable neurologic outcome was observed in 23 (19.3%). Patients with a favorable outcome have a significantly higher lung compliance (38.6 mL/cm H2O versus 27.5 mL/cm H2O), lower inspiratory pressure (12.0 cm H2O versus 16.0 cm H2O), and lower plateau pressure (17.0 cm H2O versus 21.0 cm H2O) than those with a poor neurologic outcome (all p < 0.01). Concerning time-dependent cox regression models, all maximum (adjusted hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.02–1.09), minimum (HR 1.08, 95% CI 1.03–1.13), and median (HR 1.06, 95% CI 1.02–1.09) compliances are independently associated with a good neurologic outcome. Maximum compliance, >32.5 mL/cm H2O at day 1, has the highest area under the receiver operating characteristic curve (0.745) with a positive predictive value of 90.4%. (4) Conclusions: Lung compliance may be an early predictor of intact neurologic survival in patients with ARDS following cardiac arrest.