Context Most research on sire lines is linked to growth and carcass traits. Only a limited number of field trials explore the effect of sire line on piglet vitality, litter size and the interactions between these traits. Aim The aim of this study was to examine the effect of sire line on the growth performance and vitality of progeny from birth to weaning and to evaluate the lines with respect to their impact on litter size. Methods Data included 150 litters of a Synthetic sire line (A) and 154 of a Piétrain sire line (B), with 4209 piglets born alive, which resulted from matings to 337 dams (Camborough PIC). The numbers of total born and born alive piglets per litter were recorded. Within 24 h after birth, piglet individual birthweight (BWbirth), sex (male/female) and body temperature (BT) were also recorded. At weaning, mortality rates and weaned pigs per sow were registered. At the day of weaning, 665 randomly chosen pigs were individually weighed. Weaning weights (WW) were used to calculate the weaning average daily gain (WADG). Key results Sire line significantly affected number of total born (P < 0.0001), number born alive (P < 0.01) and number of weaned pigs per sow (P < 0.01). Across lines, each additional piglet per litter resulted in a 31.2 g decline in BWbirth (P < 0.001). Larger litter sizes, higher BWbirth (P < 0.01) and piglets with a lower BT (P < 0.0001) were detected in litters of Sire line B compared with litters of Sire line A. No differences between lines were detected for WADG, WW and pre-weaning mortality (P > 0.05). A positive correlation between birthweight and WW resulted in a correspondingly higher WADG (P < 0.0001). Overall, heavier BWbirth piglets had a higher BT (P < 0.0001). Conclusions The present study indicates that Sire line B would offer a possibility to maintain litter size at a high level and, simultaneously, achieve higher BWbirth, with consequently more vital piglets. Implication It is important to emphasise that further selection for litter size in dam lines is not indicated in terms of animal welfare but also production efficiency. Instead, it seems feasible to follow the above strategy and stabilise litter size at a high level, while at the same time breeding for vitality and survivability in sire lines.