Bartonella henselae is the agent responsible for cat scratch disease (CSD). Although lymphadenopathy is typically the defining symptom, some patients develop potentially severe systemic compromise. It is unknown why some patients progress to systemic disease. The objective of this study was to describe the clinical, epidemiologic and laboratory characteristics of children with CSD and to analyze the differences between systemic versus localized infections. Patients were identified by a retrospective review of medical records at a tertiary pediatric care hospital in Buenos Aires, Argentina, from January 2012 to July 2021. A CSD case was defined as any patient who presented compatible clinical findings with a positive serologic test (IgG >1/64 or IgM immunofluorescence) for B. henselae. A total of 197 patients were identified, with a median age of 8 years (range: 1-17.4 years). The most frequent clinical symptoms were fever and lymphadenopathy. Systemic involvement was present in 34.5% (n = 68) of patients and the most common presentation was splenic abscess (n = 51), followed by liver abscess (n = 23), chorioretinitis (n = 9), osteomyelitis (n = 5) and pneumonitis (n = 3). Patients with invasive disease more frequently presented with fever (79.4% vs. 50.3%) (P<0.001) and had higher C-reactive protein levels (24.9 vs. 6.7 mg/L) (P<0.001). Antibiotic therapy was administered to 95.9% (n = 187) of patients and most with systemic disease (77%) used combination treatment. Most patients recovered fully, and there were no reported deaths. CSD must be considered a potential cause of lymphadenopathy. Patients with fever and elevated C-reactive protein should be evaluated to rule out systemic compromise.