Papaya (Carica papaya L.) is one of the few fruit crops still propagated by seeds. However, its trioecious condition and the heterozygosity of the seedlings make urgent the development of reliable vegetative propagation procedures. In this experiment, we compared, in a greenhouse sited in Almería (Southeast Spain), the performance of plantlets of ‘Alicia’ papaya originated by seed, grafting, and micropropagation. Our results show that grafted papayas were more productive than seedlings papayas (7% and 4% for total and commercial yield), while in vitro micropropagated papayas were the least productive (28 and 5% less in total and commercial yield than grafted papayas, respectively). Root density and dry weight were both higher in grafted papayas, while the seasonal production of good quality, well-formed, flowers was also enhanced in grafted papayas. On the contrary, micropropagated ‘Alicia’ plants yielded less and lighter fruit despite these in vitro plants blooming earlier and setting fruit at desirable lower trunk height. Less tall and less thick plants and reduced production of good quality flowers might explain these negative results. In addition, the root system of micropropagated papaya was more superficial, while in grafted papayas, the root system was larger and had more fine roots. Our results suggest that the cost-benefit ratio does not favor the choice of micropropagated plants unless elite genotypes are used. On the contrary, our results encourage more research on grafting, including the search for suitable rootstocks for papaya.