Background: The natural history of the progression from acute spontaneous urticaria (ASU) to chronic spontaneous urticaria (CSU), CSU remains poorly understood. Objective: To identify clinical and laboratory patient attributes that may be predictive of ASU progression to CSU. Methods: We prospectively studied consecutive adult patients (age ≥ 18 years) with a diagnosis of urticaria of <6 weeks' duration. Healthy age- and sex-matched subjects served as controls. At study entry, autologous serum skin test (ASST), complete blood cell count, erythrocyte sedimentation rate, thyroid function tests, antinuclear antibodies, antithyroglobulin and antiperoxidase antibodies, and immunoglobulin E level were assessed in all the subjects. ASST and urticaria activity score assessment were performed in all the patients at baseline and then at weeks 7, 12, 24, and 48. Results: Of 114 patients with acute urticaria and without identifiable causes, 73 patients (64%) were included in the ASU group, 41 patients in the CSU group (36%), and 44 healthy subjects in the control group. At baseline, 26 patients in the CSU group (63.4%) had a positive ASST result, whereas only 17 patients with a positive ASST result (23.3%) were revealed in the ASU group (p < 0.001). Patients with baseline ASST positive results were characterized by more profound basopenia (mean [standard deviation], 0.05 ± 0.08 cell/mm3) and more anti-thyroid peroxidase antibodies (18 [41.8%]) than those with the negative baseline ASST result (mean [standard deviation], 0.13 ± 0.09 cell/mm3, p < 0.001 more profound basopenia; and 13 (18.1%), p = 0.009 more thyroid peroxidase antibodies). We observed the disappearance of ASST positive result in some patients with CSU with baseline positive ASST results, whereas, in some subjects with CSU, baseline negative ASST results came to be positive results throughout the study period. A baseline positive ASST result of patients with ASU was a significant determinant (odds ratio 5.91 [95% confidence interval, 2.57-13.62]; p < 0.001) for a CSU diagnosis at week 7. Conclusion: The patients with ASU who progressed toward CSU were characterized by a positive ASST result, thyroid autoimmunity, and profound basopenia at baseline.