Headspace solid-phase microextraction coupled with gas chromatography and mass spectrometry detection (HS/SPME-GC/MSD) was optimized for trihalomethane (THM) determination in drinking water. A 75 μm fiber coated with carboxen/polydimethylsiloxane (75-CAR.PDMS) was used. Experimental parameters such as sample volume, time and temperature of extraction, time and temperature of desorption, magnetic stirring, and addition of sodium chloride (NaCl) were studied to determine their influence on THM extraction. Furthermore, analytical parameters such as linearity and detection limit were also evaluated. High sensitivity with detection limits in the μg/L range as well as a good linearity and reproducibility were achieved. Therefore, the HS/SPME-GC/MSD method with 75-CAR.PDMS is suitable for monitoring THMs in drinking water.