Recently, serious infections related to the use of tofacitinib (TOF) for treatment of rheumatoid arthritis (RA) have raised considerable interest. This study aimed to compare the risk for serious infections in patients with RA upon receiving TOF versus biologic disease-modifying antirheumatic drugs (bDMARDs) by age at treatment initiation. We identified adult RA patients exposed to TOF or bDMARDs using data collected by the Swiss registry for inflammatory rheumatic diseases (SCQM) from 2015 to 2018. The event of interest was the first non-fatal serious infection (SI) during drug exposure. Missing or incomplete SI dates were imputed as either the lower (left) or upper (right) limit of the known occurrence interval. The ratio of SI hazards (HR) of TOF versus bDMARDs was estimated as a function of age using covariate-adjusted Cox regression applied to each type of imputed time-to-SI. A total of 1687 patients provided time at risk for a first SI during study participation and drug exposure for 2238 different treatment courses, 345 for TOF and 1893 for bDMARDs. We identified 44 (left imputation) or 43 (right imputation), respectively, first SIs (12/12 on TOF versus 32/31 on bDMARDs). Left and right imputation produced similar results. For patients aged ≥ 69 years, the treatment HR started to be increased (lower limit of 95% confidence intervals (LLCIs) > 1). By the age of 76, the difference between TOF and bDMARDs started to be clinically relevant (LLCIs > 1.25). For patients aged < 65 years, the data were insufficient to draw conclusions. Our results suggest that we should expect an increased risk for SIs in older patients treated with TOF compared to bDMARDs supporting a cautious use of TOF in these patients.