Limitations of live oocyst anticoccidial vaccines in poultry have led to a search for the new generation of anticoccidial vaccines. Several sources may influence the protective efficacy of the new generation of anticoccidial vaccine candidates. Therefore, the objective of this study was to explore the sources influencing the protective efficacy (in terms of the lesion score and the oocyst output) of the new-generation anticoccidial vaccine candidates from the challenge trials in chickens, using meta-analysis techniques. The overall effect size was also estimated to get the overview of the protective efficacy. The study outcomes were the standardized mean difference (SMD) of the lesion score and the difference in mean (DM) of the oocyst output. Descriptive statistics of the oocyst decrease ratio (%) and anticoccidial index (ACI) were also presented. Relevant citations were retrieved from PubMed, Scopus, and Web of Science. Of 1524 retrieved citations, 63 were included for meta-analysis (60 for the lesion score and 44 for the oocyst output). Overall, the new generation of anticoccidial vaccine candidates partially protected chickens from coccidiosis because they significantly reduced the lesion score (SMD = −3.69, [95% CI: −4.08 to −3.29], P < 0.001) with high heterogeneity (I2 = 96.85%) and the oocyst output (DM = −1.48, [95% CI: −1.75 to −1.21], P < 0.001) with high heterogeneity (I2 = 99.69%). The median oocyst decrease ratio was 66.15% (a range from 4.27% to 95.93%, n = 125 subgroups). The median ACI was 164.71 (a range from 50.05 to 196.40, n = 115 subgroups). Vaccine platform and route of administration were identified as sources of heterogeneity for the lesion score and the oocyst output. However, severe publication bias threatened validity of the lesion score outcome. After accounting for other sources of variation, the anticoccidial vaccine candidates were shown to be less effective in reducing the oocyst output when the challenge dose, the length between the day of last immunization and the day of the challenge, or the length between the day of the challenge and the day of sampling, increased. In conclusion, although the new generation of anticoccidial vaccine candidates clearly showed a partial protection of chickens from coccidiosis in experimental trials, the protective efficacy was influenced by several sources, such as the vaccine platform and route of administration. Sources of high heterogeneity such as protein antigens are worth exploring when additionally relevant data are available. Therefore, additional experimental trials in chickens are required to better understand the protective efficacy of the new-generation anticoccidial vaccine candidates.