Peste des Petits Ruminants (PPR) is a highly infectious disease caused by a virus of the Morbillivirus genus. The current PPR eradication effort rely mainly on the implementation of massive vaccination campaigns. One of the most widely used PPR vaccine is the Nigeria 75/1 strain obtained after attenuation by 75 serial passages of the wild type isolate in cell cultures. Here we use high throughput deep sequencing on historical passages that led to the Nigeria 75/1 strain, to follow the evolution of PPRV attenuation and assess risk of reversal in different cell types. Comparison of the consensus sequences for the wild type and vaccine strain showed that only 18 fixed mutations separate the two strains. At the earliest attenuation passage at our disposal (passage 47), 12 out of the 18 mutations were already present with 100% frequency. Low frequency variants were identified along the genome for all passages. Sequencing of passages posterior to the vaccine strain showed evidence of genetic drift during cell passages, especially in cell expressing the SLAM receptor targeted by PPRV. However, 15 out of 18 mutations related to attenuation remained fixed in the population. In vitro experiments suggest that one mutation in the leader region of the PPRV genome affects virus replication. Our study suggest that only few mutations can have a serious impact on the pathogenicity of PPRV. Risk of reversal of PPRV strain Nigeria 75/1 after serial passages in cell cultures seems low but limiting the number of passages during vaccine production is recommended.