Clinical stability (CS), defined as normalization of vital signs, is often used to manage inpatients with community-acquired pneumonia (CAP). The main objective of our study was to identify a reliable definition of CS for human immunodeficiency virus (HIV)-positive patients with CAP. During an 18-month period, 437 HIV-positive Italian inpatients with CAP were enrolled in the study. We used 3 definitions of CS (from a less conservative [definition 1] to a more conservative [definition 3] definition) based on combinations of different thresholds for vital signs. Assessments were performed at admission and daily during the hospital stay. For the 3 definitions, 14.9%, 8.0%, and 4.8% of patients were stable at baseline, with deterioration after reaching CS in 7.16%, 4.76%, and 2.05%, respectively. The 8 patients whose conditions deteriorated after reaching CS definition 3 (systolic blood pressure, >90 mm Hg; pulse, <90 beats/min; respiratory rate, <20 breaths/min; oxygen saturation, >90%; temperature, <37 degrees C; ability to eat; and normal mental status) survived and were discharged from the hospital. The more conservative definition of CS appears to be reliable for the management of HIV-infected patients with CAP.