Objective: To investigate the two-year survival rate of primary molars treated with non-instrumentation endodontic treatment with mixed antibiotic paste containing chloramphenicol, tetracycline, zinc oxide and eugenol (CTZ pulpotomy), and compare it to the conventional root canal treatment with calcium hydroxide paste. Material and Methods: Thirty-six children, mean age 6.2 years old (standard deviation, SD=1.5), presenting at least one primary molar with irreversible pulpitis or necrotic pulp, were included in this prospective clinical study. Teeth were assigned to CTZ pulpotomy (Group I) or calcium hydroxide pulpectomy (Group II) and assessed clinically and radiographically for up to 26 months. Data were analyzed using descriptive statistics, Chi-square test, Kaplan-Meier survival analysis and Log-rank test. Results: Fifty-three primary molars were treated in Group I (n=37) or Group II (n=16). Children were followed up for 1 to 26 months (mean=12.0; SD=7.1). Treatment failure rates were 73.0% in Group I and 31.3% in Group II. Overall, mean survival time was 15.2 months (95% confidence interval, CI 12.6-17.9); Group I (mean 13.2; 95% CI 10.2-16.3) had a lower survival rate than Group II (mean 18.9; 95% CI 14.5-23.2) (p=0.02). Necrotic pulp treatments had significantly lower survival rates (p=0.01) than pulpitis treatments. Conclusion: Non-instrumentation endodontic treatment of primary molars with CTZ paste resulted in a low survival rate in a two-year follow-up; its radiographic ineffectiveness discourages its use instead of conventional root canal endodontic treatment.