Aim The aim of the study was to define and compare persistence of infliximab and adalimumab according to the treatment line. The secondary objectives were to identify factors that influence persistence. Methods We performed an observational, retrospective, single-center study with adult patients diagnosed with Crohn’s disease between November 2001 and May 2020. A total of 309 patients were included. Survival analysis and Cox regression were used. The following factors were studied: gender, body mass index, use of concomitant immunosuppressants, time from diagnosis to the beginning of the biological, trough drug levels on target, year where the anti-TNFα began and initial patient characteristics at the beginning of the treatment. Results The median persistence associated with the first-line of anti-TNFα treatment showed a statistically significant difference with respect to the second-line (7.0 vs 5.2, p= 0.0082). Differences between infliximab and adalimumab were not statistically significant (7.8 vs 6.5, p= 0.91). The multivariate Cox analysis shows that only drug concentrations on target and year of initiation of anti-TNFα were associated with higher persistence in first-line treatment (p= 0.04). In the second-line the difference between the infliximab and adalimumab subgroups was not statistically significant (5.1 vs 5.2, p= 0.5). Only the year of initiation of treatment showed an influence on persistence. Conclusion Persistence was greater in the first-line. No differences in persistence were observed between infliximab and adalimumab. The most important influencing factors were the year of initiation of treatment and target drug concentrations.