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Despite effective vaccination schedules employed in the control of Newcastle disease (ND) in Ghana, the preponderance of ND outbreaks is still high. This study was therefore carried out to compare booster effects of inactivated ND vaccine and thermostable ND I-2 vaccine in layers and its impact on egg production at a private farm in Kumasi, Ghana. Thirty thousand layers (10,000 per group) of 36 weeks old were used for the study. Group C was vaccinated with inactivated ND vaccine (Nobilis Newcavac, South Africa), Group D with ND I-2 vaccine and Group F was the control group, which was not vaccinated. Antibody titres of the birds were determined 10 days and a day before vaccination and from day 4 to day 28 after vaccination using haemagglutination-inhibition (HI) test and the mean titres were calculated. Both inactivated ND vaccine and thermostable ND I-2 vaccine produced booster responses. The inactivated ND vaccine produced a higher average titre increase of 37.20 % compared to ND I-2 vaccine, 33.33 %. Average titres of the control population reduced by 24.26 %. Egg production reduced by 8 % and 3 % in populations vaccinated with inactivated ND vaccine and ND I-2 vaccine respectively. In conclusion, inactivated ND vaccine and the thermostable ND I-2 vaccine produced booster effect with ND I-2 causing minimal reduction in egg production, indicating that the use of easily applicable ND I-2 vaccine should be encouraged.