Despite the high prevalence of antimicrobial-resistant Escherichia coli in hospital-acquired infections, the clinical epidemiology of fluoroquinolone (FQ) resistance in community-onset spontaneous bacterial peritonitis (SBP) in patients with cirrhosis is not well understood. This study was performed to evaluate clinical features and risk factors for community-onset SBP caused by FQ-resistant E. coli. A case-control control study was performed using cases of community-onset SBP from June 2000 to August 2011 at Samsung Medical Center (Seoul, Korea). Patients with FQ-resistant E. coli were designated as case patients. A control group I (CG I) patient was defined as a person whose clinical sample yielded FQ-susceptible E. coli, and a control group II (CG II) patient was defined as a person with a negative culture result. A total of 82 subjects with community-onset SBP caused by E. coli were identified, of which 26 (31.7%) were FQ-resistant E. coli infection. Fifty-seven matched subjects were randomly selected for CG II. Compared with CG I, previous SBP episodes (OR, 4.91; 95% CI, 1.50-16.53; P = 0.010), prior use of FQ within 30 days (OR, 7.05; 95% CI, 1.17-42.38; P = 0.033), and third-generation cephalosporin resistance (OR, 17.68; 95% CI, 1.67-187.26; P = 0.017) were significantly associated with FQ-resistant E. coli. Compared with CG II, a previous SBP episode was significantly associated with FQ-resistant E. coli (OR, 4.20; 95% CI, 1.50-11.80; P = 0.006). FQ-resistant E. coli is a significant cause of community-onset SBP, with relation to previous SBP episodes, recent FQ use and third-generation cephalosporin resistance.