Purpose: The aim of this study is to examine the effectiveness of the neutrophil-lymphocyte ratio (NLR) and CRP/albumin ratio (CAR) in evaluating disease severity and predicting clinical outcomes in patients diagnosed with acute cholecystitis (AC). Methods: A total of 186 patients with AC were evaluated retrospectively. NLR, CAR, Mannheim Peritonitis Index (MPI), and P-POSSUM (Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity) scores were compared with AC severity grade. Results: The rates of the grade 1 patients (group 1) and the grade 2–3 patients (group 2) were 57.5% (n = 107) and 42.5% (n = 79) according to the disease severity according to Tokyo Guidelines criteria (TG) 18/TG13, respectively. The morbidity rates determined in groups 1 and 2 were 26.7% (n = 28) and 51.9% (n = 41), respectively. No mortality was found in group 1, whereas the mortality rate in group 2 was 6.3% (n = 5). According to multivariate analysis, CAR (odds ratio [OR], 1.234; P < 0.001) and MPI (OR, 1.175; P = 0.001) were found to be associated with moderate-severe disease while CAR (OR, 1.109; P = 0.035) and P-POSSUM morbidity (OR, 1.063; P = 0.007) variables were found to be associated with the presence of morbidity. Conclusion We have demonstrated that CAR can be used in predicting severity of AC and that CAR is an alternative simple parameter of P-POSSUM morbidity score in prediction of morbidity in these cases. In addition to other assessment methods, these scores can provide valuable and complementary information in assessment of disease severity and prognosis in AC.