Mediterranean spotted fever (MSF) is a rickettsial disease caused by Rickettsia conorii, transmitted by brown dog ticks, and endemic in the Mediterranean region. Its incidence is increasing, with varied presentations and potential complications because of delayed diagnosis. This study retrospectively included 173 adult patients hospitalized for MSF at La Rabta University Hospital, Tunis, from 2000 to 2020. Patients, predominantly male (67.6%) and averaging 40 years of age, mostly resided in urban areas (82.7%). Animal exposure was reported in 74.6%, and cases peaked during the hot season (68.8%), with no cases in winter months. The classic triad of fever, rash, and eschar was observed in 69.9%, with maculopapular lesions affecting palms and soles in 83.8%. Headache (64.5%), myalgia (60.7%), and arthralgia (57.2%) were also common. Laboratory findings included elevated white blood cell count (36.4%), thrombocytopenia (48%), and increased aspartate aminotransferase (50.9%). Treatment with doxycycline (n = 161) resolved fever within 2.8±1.3 [1–5] days. Complications, including encephalitis, chorioretinitis, anterior uveitis and vasculitis, occurred in 2.3% of cases, but all patients recovered without relapse. No significant risk factors for severe forms were identified. Improved awareness of MSF’s clinical features may be the key to an early diagnosis and successful treatment.