Background and objectives: To investigate the risk factors for emphysematous cystitis (EC) compared to those of acute cystitis (AC) to increase clinicians awareness of the possibility for the aggravation of patient status. Materials and methods: We retrospectively reviewed a total of 54 patients who were hospitalized with a diagnosis of EC by abdominal computed tomography (CT) scan from 2006 to 2020. The control group included 92 patients who were hospitalized for the treatment of AC in the same period. We sought to identify the clinical features and predisposing diseases, such as age, sex, diabetes mellitus (DM), hypertension (HTN), cerebrovascular accident (CVA), chronic kidney disease (CKD), neurogenic bladder (NB), history of urinary tract infection (UTI), and emphysematous pyelonephritis (EPN), that were associated with the development of EC. Results: The median (interquartile range (IQR)) age of the patients with EC was older than that of the patients with AC (78.5 (15.3) years (range: 52–100) vs. 70.0 (26.5) years (range: 28–97 years)). Sepsis and mortality occurred only in the EC group (48.1% and 11.1%, respectively). The univariate analysis of predisposing factors revealed that age, DM, HTN, CVA, CKD, and NB were significantly associated with EC. In the multivariate analysis, DM (OR, 6.251; 95% CI, 2.254–17.250; p < 0.001), CKD (OR, 18.439; 95% CI, 3.421–99.404; p = 0.001), NB (OR, 7.374; 95% CI, 1.993–27.285; p = 0.003) were associated with EC. Conclusions: The results of this study revealed that DM, CKD, and NB were significant risk factors for EC. The tendency toward sepsis and high mortality underscore the need for careful observation while treating patients with EC with the risk noted above.