Objectives This prospective study was aimed to determine and quantify the change in mandibular condylar hyperactivity over a period of time by using a fluorine-18 (18F) fluoride PET-computed tomography (CT) scan. Materials and methods Sixteen patients (age 19.50±2.58 years) with noticeable faciomandibular asymmetry caused by unilateral condylar hyperplasia (UCH) were included in the test group and underwent an 18F-fluoride PET-CT scan at the beginning of the study (T0); these patients were then followed up for a minimum of 12 months, after which the 18F-fluoride PET-CT scan was repeated at first follow-up (T1). An age-matched control group consisted of 10 patients with apparently symmetrical faces whose PET-CT scans were acquired for some other medical conditions. Statistical analysis of maximum standardized uptake values (SUV max) obtained through 18F-fluoride PET-CT was performed using the paired t-test. Results Mean SUV max of the affected condyle at T0 and T1 was 9.18±4.07 and 9.18±3.88, respectively. The mean SUV max of the contralateral condyle at T0 and T1 was 6.21±2.30 and 6.66±2.64, respectively. The mean right-left difference in tracer uptake between the test and control groups both at T0 and T1 was statistically significant. Right-left percentage difference of isotope uptake of the test group was 16.87±15.75% at T0 and 14.97±12.72% at T1. Right-left percentage difference of isotope uptake of the control group was 5.51±5.72%. Although these differences were statistically significant, their clinical relevance was insignificant. SUV max of the higher uptake side and the lower uptake side of the control group was 5.63±1.85 and 5.09±1.83, respectively. Conclusion Great diversity exists in the clinical presentation of UCH. The growth trend of UCH is highly variable because of the age and sex of patients. The results of the present study show that the 18F-fluoride PET-CT scan may guide us in determining the right time and in making the right choice of surgico-orthodontic intervention in UCH patients. The clinical presentation and SUV max of PET-CT of UCH patients were in agreement with each other. The baseline values of the control group indicated that these could also be used to differentiate normal from abnormal condylar growth in potential class III skeletal pattern cases-that is, patients having sagittal skeletal dysplasia resulting from either maxillary deficiency or mandibular protrusion, or both in combination, thus resulting in a concave facial profile.