In vivo antimicrobial resistance has yet to be documented in Chlamydia trachomatis; however, there have been anecdotal reports of persistent infection. The purpose of this case series was to describe a group of patients who have persistent chlamydia infection despite adequate treatment and where re-infection was considered unlikely. Patients were selected using a clinical questionnaire. For inclusion patients had to have tested positive for C. trachomatis, at least twice, using a nucleic acid amplification test despite having been fully compliant with at least two rounds of recommended therapy and be deemed to be at low risk of re-infection. Patients were grouped into categories based on sexual behaviour. Twenty-eight patients are included in this case series; 46 declared no sexual contact since initial diagnosis (category 1), a further 36 declaring contact that was considered low risk of re-infection (categories 24); 61 showed signs and symptoms at initial presentation increasing to 75 at re-attendance. Thirty-nine percent of patients received azithromycin only while 48 received doxycycline also. This case series identifies patients with persistent chlamydia despite receiving treatment. There is a need for a case definition of clinical treatment failure, development of susceptibility testing methods and guidance on appropriate treatment for patients with persistent infection.