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Under UK legislation, nurses independently prescribe or supply medications using PGDs, but evidence on safety in clinical practice is limited.Clinical record review across five UK sexual health services, July–December 2015. Sample size quota stratified based on the number of INP/PGD practising nurses. Documented patient presentations, diagnoses, autonomy and safety/appropriateness of medication delivery were compared between INP and PGDs.From 1,851 (INP=711, 38%; PGD=1,140, 62%) clinical records, 50% (n=933) involved medication delivery. INP delivered medication more frequently (INP= 385/711, 54% vs. PGD=548/1,140, 48%; p=0.01). A total of 879 medication assessments were undertaken (INP=399, PGD=480), 69% (n=609/879) were ‘new’ care episodes. Past medical history, concurrent medications and allergy risk assessments were recorded >85% (n=755/879) of cases. INP managed more symptomatic presentations (n=181/399, 45%: asymptomatic n=121/399, 30%); PGD managed marginally more asymptomatic (n=221/480, 46%; symptomatic n=200/480, 42%). INP worked more autonomously than PGDs (INP=310/399, 78%; PGD=308/480, 64%, p<0.01). INP most frequently managed chlamydia (n=53/399, 13%), PGDs most frequently administered vaccinations (n=80/480, 17%). Nurses delivered 66 different products, 1,351 individual medicines, azithromycin being most common (n=231/1351, 17%). Overall, 88% (n=775/879) of episodes were assessed against guidelines as ‘safe and appropriate’ (INP=359/399, 90%; PGD=416/480, 87%). Main reason for not ‘safe and appropriate’ was lack of documentation (n=56/104, 54%). PGDs were, although clinically appropriate, used outside their limits in 5% (n=24/480) of consultations.INP deliver medications more frequently and work more autonomously than PGD users. Both groups were comparable in safe/appropriate medication delivery. Improved documentation is recommended.