Background Papua New Guinea (PNG) has one of the highest prevalences of HIV and sexually transmissible infections (STIs) in the Asia-Pacific region, and one of the highest burdens of maternal syphilis and cervical cancer globally. Despite this disease burden, only limited clinical research in sexual and reproductive health has been conducted in PNG. Methods: A longitudinal clinical cohort study was conducted at two sexual health clinics. Participants completed a behavioural interview, clinical assessment and genital examination at baseline, and at 12, 24 and 50 weeks, including specimen collection for STI diagnostics. Results: In total, 154 people attended a screening visit. Reattendance at 12, 24 and 50-weeks was 87%, 78% and 80% respectively. At baseline, HIV prevalence was 3.3%; chlamydia (Chlamydia trachomatis), 29.2%; gonorrhoea (Neisseria gonorrhoeae), 22.1%; Trichomonas vaginalis 15.6%; herpes simplex type-2 (HSV-2), 46.1%; active syphilis, 11.7%. Multiple infections were common particularly among women. The incidence of chlamydia was 27 per 100 person-years (PY); gonorrhoea, 15 out of 100 PY; T. vaginalis, 29 out of 100 PY; HSV-2, 12 out of 100 PY; syphilis, 8 out of 100 PY. No incident HIV cases were recorded. At baseline, 39% of men in Mt Hagen and 65% in Port Moresby had a penile foreskin cut, with a dorsal slit being the most common. Two men underwent penile cutting during the follow-up period. Conclusions: The prevalence and incidence of STIs, HIV and penile cutting were high among sexual health clinic attendees. High retention figures suggest that this population may be suitable for future interventions research and clinical trials.