Abstract The effectiveness of depuration for the removal of hepatitis A virus (HAV), norovirus (NoV) genogroups I (GI) and II (GII), and F+RNA bacteriophage (F+RNA) was evaluated for pullet carpet shell clams (Venerupis pullastra) and Mediterranean mussels (Mytilus galloprovincialis). The objective was to compare the behaviour of the different pathogens under commercial depuration conditions during 7 days in an authorized plant. Standard double agar overlay method (ISO 10705-1) was employed for F+RNA quantification. Recently developed ISO/TS 15216:2013 standard method, based on RT-real time PCR, were employed for the quantification of HAV and NoV. The reduction of F+RNA showed a two-phase depuration kinetic. The average reduction rates were 1-log units for clams and 2-log units for mussels, with residual levels after the process of 6.3 × 103 and 8.3 × 101 F+RNA/100 g, respectively. HAV, NoV GI and GII were detected intermittently throughout the entire process, ranging mostly from 103 to 105 RNA copies/g digestive tissue (DT). NoV GI showed the higher viral levels followed by NoV GII and HAV. All of them were detected in clams after seven days of depuration, however, in mussels only NoV GI was detected after the process. Generally, clams showed slower depuration rates and higher contamination levels for all viruses analysed.