Understanding the uptake and accumulation of pharmaceuticals in vegetables under typical irrigation practices is critical to risk assessment of crop irrigation with reclaimed water. This study investigated the pharmaceutical residues in greenhouse lettuce under overhead and soil-surface irrigations using pharmaceutical-contaminated water. Compared to soil-surface irrigation, overhead irrigation substantially increased the pharmaceutical residues in lettuce shoots. The increased residue levels persisted even after washing for trimethoprim, monensin sodium, and tylosin, indicating their strong sorption to the shoots. The postwashing concentrations in fresh shoots varied from 0.05 ± 0.04 μg/kg for sulfadiazine to 345 ± 139 μg/kg for carbamazepine. Root concentration factors ranged from 0.04 ± 0.14 for tylosin to 19.2 ± 15.7 for sulfamethoxazole. Translocation factors in surface-irrigated lettuce were low for sulfamethoxalzole, trimethoprim, monensin sodium, and tylosin (0.07-0.15), but high for caffeine (4.28 ± 3.01) and carbamazepine (8.15 ± 2.87). Carbamazepine was persistent in soil and hyperaccumulated in shoots.