The aim of this study was to determine whether there is an association between flexor digitorum and lumbrical muscle intrusion into the carpal tunnel and carpal tunnel syndrome (CTS). Five hundred thirteen manual laborers (1026 wrists) were evaluated with ultrasound to determine whether those with CTS had more muscle intrusion into the carpal tunnel than those without CTS. One hundred ninety of the participants without CTS at baseline (363 wrists) were followed over 1 year to determine whether muscle intrusion at baseline predicted the development of CTS. Participants with CTS had more muscle within the carpal tunnel with the wrist in the neutral (P=0.026) and flexed (P=0.018) positions than those without CTS. Baseline muscle intrusion did not predict development of CTS at 1 year. Muscle intrusion into the carpal tunnel is associated with CTS, but muscle intrusion alone does not predict the development of CTS over the course of a year.