Introduction Multiple expert panels at Kaiser Permanente approved infliximab-dyyb (Inflectra®), a biosimilar to the reference product infliximab (Remicade®), to be the preferred infliximab agent for therapeutic substitution from infliximab for adult patients with dermatologic, rheumatologic, and/or gastroenterologic diagnoses. The objective of this study was to assess the safety and effectiveness of infliximab-dyyb for Kaiser Permanente Northern California patients with psoriatic and rheumatoid arthritis who switched from infliximab to infliximab-dyyb. Methods This was an observational, data-only, non-inferiority study assessing adult patients with a rheumatologic condition of psoriatic arthritis (PsA) or rheumatoid arthritis (RA) who were switched from infliximab to infliximab-dyyb or used infliximab continuously in the Northern California region of Kaiser Permanente from May 2017 through May 2018. Both groups were followed for 12 months. The primary effectiveness outcome was disease worsening requiring acute care defined as emergency room visit or hospitalization related to the rheumatologic condition or orthopedic surgery intervention. Non-inferiority was set at an upper limit of 4%. Results A total of 70 individuals were identified as continuing infliximab and 727 individuals were switched to infliximab-dyyb. There were 2 patients (2.9%) in the infliximab group and 22 patients (3.0%) in the infliximab-dyyb group who experienced disease worsening requiring acute care (P = 0.03 for non-inferiority). Conclusion There was no increased risk of disease worsening requiring acute care in patients with RA or PsA who switched from infliximab to infliximab-dyyb when compared to patients who remained on infliximab in this population.