Objective To compare the short-term effects of single-visit and multi-visit root canal therapy for infected root canals. Methods One hundred and thirty patients (143 teeth) with acute and chronic periapical inflammation or pulp necrosis were randomly divided into single-visit root canal therapy group (n=95, root canal preparation and filling in one visit) and multi-visit root canal therapy group (n=48, conventional root canal therapy with 1 to 2 subsequent visits). Twenty-four hours after root canal filling (single-visit root canal therapy group) or intracanal medication in first visit (multi-visit root canal therapy group), the pain degree was self-assessed by patients with visual analogue scale (VAS). In single-visit root canal therapy group, subsequent visit was done 1 week after root canal filling, and the pain degree was clinically evaluated. In multi-visit root canal therapy group, the pain degree was clinically evaluated during subsequent visits 1 week after intracanal medication and 1 week after root canal filling respectively. Six months and 1 year after root canal filling, the therapeutic effect was determined with X-ray examination and clinical assessment. Results There was no significant difference in the degree of pain self-assessed by patients (P>0.05), and the incidences of acute reaction were 10.53% and 12.5% in single-visit root canal therapy group and multi-visit root canal therapy group respectively (P>0.05). There was no significant difference in the degree of pain in clinical evaluation (P>0.05). Six months and 1 year after root canal filling, the cure rates were 83.3% and 88.5% in single-visit root canal therapy group, and those were 88.9% and 90.5% in multi-visit root canal therapy group, with no significant difference between two groups (P>0.05). Conclusion For infected root canals, single-visit root canal therapy may yield similar short-term postoperative pain and therapeutic effect with multi-visit root canal therapy.