BackgroundClinicians in areas where malaria and typhoid fever are co-endemic often treat infected patients irrationally, which may lead to the emergence of drug resistance and extra cost to patients. This study determined the proportion of febrile conditions attributable to either malaria and/or typhoid fever and the susceptibility patterns ofSalmonellaspp. isolates to commonly used antimicrobial agents in Ghana.MethodsOne hundred and fifty-seven (157) febrile patients attending the Ga West Municipal Hospital, Ghana, from February to May 2017 were sampled. Blood samples were collected for cultivation of pathogenic bacteria and the susceptibility of theSalmonellaisolates to antimicrobial agents was performed using the Kirby-Bauer disk diffusion method with antibiotic discs on Müller Hinton agar plates. For each sample, conventional Widal test for the detection ofSalmonellaspp was done as well as blood film preparation for detection ofPlasmodiumspp. Data on the socio-demographic and clinical characteristics of the study participants were collected using an android technology software kobo-collect by interview.ResultsOf the total number of patients aged 2–37 years (median age = 6 years, IQR 3–11), 82 (52.2%) were females. The proportion of febrile patients with falciparum malaria was 57/157 (36.3%), whileSalmonella typhiO and H antigens were detected in 23/157 (14.6%) of the samples. The detection rate ofSalmonellaspp in febrile patients was 10/157 (6.4%). Malaria and typhoid fever coinfection using Widal test and blood culture was 9 (5.7%) and 3 (1.9%), respectively. The isolates were highly susceptible to cefotaxime, ceftriaxone, ciprofloxacin, and amikacin but resistant to ampicillin, tetracycline, co-trimoxazole, gentamicin, cefuroxime, chloramphenicol, and meropenem.ConclusionPlasmodium falciparumandSalmonella sppcoinfections were only up to 1.9%, while malaria and typhoid fever, individually, were responsible for 36.3% and 6.4%, respectively. Treatment of febrile conditions must be based on laboratory findings in order not to expose patients to unnecessary side effects of antibiotics and reduce the emergence and spread of drug resistance against antibiotics.