A   mixture  of  acamprosate calcium, disulfiram and ondansetron hydrochloride   is used for the   treatment of   drug abuse including alcoholism. In this study, a UV- spectrophotometric method was proposed for simultaneous determination of acamprosate calcium, disulfiram and ondansetron hydrochloride.  Determination of these drugs was performed using the 1D value of acamprosate calcium at 207 nm, 2D value of disulfiram at 270 nm and 3D value of ondansetron hydrochloride at 310 nm. The  analysis  method  was validated for various parameters according to ICH guideline and linear  over  the  range  of  8-48,4-24, and  2-12  µg ml-1 for acamprosate calcium,   disulfiram  and ondansetron hydrochloride, respectively.  The correlation coefficient was found to be 0.998, 0.998 and 0.999 for ACM, DIS and OND respectively. Within-day and between-day precision and accuracy values for all three compounds were within an acceptable range .The developed method was used for simultaneous determination of these drugs in pharmaceutical individual dosage forms and in laboratory mixture no interference from excipients was observed.