The purpose of this study was to evaluate clinical outcome differences of root canal obturation by warm gutta-percha (GP) or cold lateral condensation (CLC) through a systematic review and meta-analysis. There were 10 clinical studies evaluated. Postoperative pain, long-term outcomes, obturation quality, and overextension were the characteristics investigated. The results suggest that the two obturation techniques are not significantly different except in overextention. The relative risk (RR) value of warm GP versus CLC and 95% confidence interval (CI) of the first three criteria were 1.10 (0.71, 1.71), 0.78 (0.58, 1.05), and 1.31 (0.98, 1.76), respectively. Overextension was more likely to occur in the warm GP obturation group in comparison with the CLC group. The RR value and 95% CI were 1.98 (1.33, 2.93). In conclusion, warm GP obturation demonstrated a higher rate of overextension than CLC. Postoperative pain prevalence, long-term outcomes, and obturation quality were similar between the two groups.