Alternative strategies are applied for the prevention of Necrotic Enteritis (NE) particularly after the global perspective of the antibiotic ban. This study was a trial for NE control depending on vaccination by toxoid and/or immune enhancement by Nutri-lac IGA administration (a liquid mixture of fermentation by-product 80%, lactic acid 10%, and formic acid 10%). A total of 120 one-day-old broiler chicks were randomly divided into four groups (30 chicks/group). Group 1 (G1) was vaccinated with C. perfringens type A toxoid; Group 2 (G2) was toxoid-vaccinated and immune enhanced by Nutri-Lac IGA; Group 3 (G3) was immune enhanced by Nutri-Lac IGA and Group 4 served as control. Each group was subdivided into two subgroups, one subgroup was challenged with C. perfringens and the other was kept unchallenged. No significant clinical signs were detected in birds and mortality was observed only among challenged controls. The thin and friable intestinal wall was observed in all challenged broilers which extended to ulceration only in the challenged control group. No prominent histopathological findings related to NE were detected except in challenged controls and the highest protection against the NE-histopathological changes vividly appeared in the challenged G2 group. Significant increase in body weight of G1 and G2 groups after challenge in comparison to before challenge. While body weight of chickens in both G3 and challenged control groups was lower after challenge than before challenge. Pre-challenge ELISA results indicated no significant difference in immunoglobulin (Ig) Y titer among all groups after the first dose of vaccination, while significant differences appeared after the booster dose. The highest IgY titer was recorded in the G2 group, followed by G1, and G3 group. Post-challenge ELISA results showed a highly significant difference among all challenged subgroups. The highest IgY titer was recorded in the G1, followed by G2, and G3 group. The serum neutralization test also demonstrated the highest mean antibody titer in G1 and G2 groups. In conclusion, this study confirmed that a toxoid-immunostimulant combination is effective in NE prevention only when it is accompanied by the absence of NE predisposing factors.