Lymphedema related to lymphatic filariasis (LF) is a disabling condition that commonly manifests in adolescence. Fifty-three adolescents, 25 LF infected and 28 LF non-infected, in age and sex-matched groups, using the Binax ICT rapid card test for filarial antigen were recruited to the study. None of the participants had overt signs of lymphedema. Lymphedema assessment measures were used to assess lower limb tissue compressibility (tonometry), limb circumference (tape measure), intra- and extra-cellular fluid distribution (bioimpedance) and joint range of motion (goniometry). The mean tonometric measurements from the left, right, and dominant posterior thighs were significantly larger in participants with LF compared to participants who had tested negative for LF (p = 0.005, p = 0.004, and p = 0.003, respectively) indicating increased tissue compressibility in those adolescents with LF. ROC curve analysis to define optimal cut-off of the tonometry measurements indicated that at 3.5, sensitivity of this potential screening test is 100% (95%-CI = 86.3%, 100%) and specificity is 21.4% (95%-CI = 8.3%, 41.0%). It is proposed that this cut-off can be used to indicate tissue change characteristic of LF in an at-risk population of PNG adolescents. Further longitudinal research is required to establish if all those with tissue change subsequently develop lymphedema. However, thigh tonometry to identify early tissue change in LF positive adolescents may enable early intervention to minimize progression of lymphedema and prioritization of limited resources to those at greatest risk of developing lifetime morbidity.