Background: The objective of the study was to compare the efficacy and safety of ketoprofen patch versus diclofenac patch as post-operative analgesic in hysterectomy patients.Methods: The study was a prospective, single blind, randomized, comparative interventional clinical study conducted in a tertiary care hospital. Sixty female patients were randomly allocated to receive either ketoprofen or diclofenac patch 1 hour prior to the hysterectomy. Pain was assessed postoperatively after an interval of every four hours for 24 hours using visual analogue scale (VAS) and verbal rating scale (VRS).Results: In ketoprofen group, mean VAS was (2.92±0.11) significantly low as compared to diclofenac group (3.25±0.14). The mean VRS score in group ketoprofen (1.62±0.22) was low as compared to group diclofenac (1.83±0.16). Safety analysis revealed no apparent serious adverse events. Inj. Paracetamol 1 gm i.v was given as rescue analgesic to the patients in whom VRS >2 and VAS >5 was noted. Data were analysed using unpaired student’s t-test.Conclusions: Transdermal patches are very convenient to use and causes less discomfort as compared to traditional routes of drug delivery. Ketoprofen patch was found better in providing analgesia after hysterectomy as compared to diclofenac patch with lesser side effects.