In rabies endemic areas, appropriate management of dog bites is critical in human rabies prevention. Victims must wash bite wounds for 15 minutes with soap, water and disinfectant immediately before seeking medical care. This study investigated the epidemiology of dog bites and determinants of compliance to these preclinical guidelines requirements among dog bite victims from high rabies-burden areas of Wakiso and Kampala, Uganda. An explanatory sequential mixed-methods study design was used. Quantitative data were collected from 376 dog-bite patients at two healthcare facilities. Qualitative data as also collected through 13 in-depth interviews with patients, healthcare workers, herbalists and veterinarians. Qualitative data were analyzed using a deductive thematic approach. Generalized lineal models were used to determine factors associated with compliance. Nearly half (190, 51%) of the patients were from Wakiso District and 293 (77.9%) had grade II wounds. Most of the wounds (171, 45.5%) were on the legs. Two thirds of the bites occurred in public places. Only 70 (19%) of the bite patients had complied with preclinical guidelines. Nearly half of the patients had applied unrecommended substances such as herbs (47/193), antiseptics (46/193), black stone (25/193) and unknown creams (10/193) on the wounds. Factors negatively associated with compliance included: being aged 15 years or older, adjPR = 0.70 (0.47,0.92) and knowing the dog owner, adjPR=0.65 (0.36,0.93). However, attainment of secondary or higher education, adjPR= 1.76 (1.24,3.79), being in employment, adjPR = 1.48 (1.09,2.31), perception that the dog was sick, adjPR = 1.47 (1.02,2.72) and knowledge about the subsequent victim(s) of the dog adjPR=0.35 (0.17,0.70) were positively associated with compliance. High occurrence of dog bites in public places by free-roaming dogs suggests the need for promotion of responsible dog ownership. Additionally, targeted health education may be required to improve the low compliance to preclinical guidelines.